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Kitamura K, Arita M. Evaluation of VP4-VP2 sequencing for molecular typing of human enteroviruses. PLoS One 2024; 19:e0311806. [PMID: 39656727 DOI: 10.1371/journal.pone.0311806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 09/25/2024] [Indexed: 12/17/2024] Open
Abstract
Enteroviruses and rhinoviruses are highly diverse, with over 300 identified types. Reverse transcription-polymerase chain reaction (RT-PCR) assays targeting their VP1, VP4, and partial VP2 (VP4-pVP2) genomic regions are used for detection and identification. The VP4-pVP2 region is particularly sensitive to RT-PCR detection, making it efficient for clinical specimen analysis. However, a standard type identification method using this region is lacking. This study aimed to establish such a method by examining the divergence of VP4-pVP2 amino acid sequences between enterovirus and rhinovirus prototypes. Pairwise analysis of 249 types indicated a 95% threshold for enterovirus intra-species identification but not for rhinovirus prototypes. Protein BLAST search analyses of representative enterovirus prototypes, including EV-A71, EV-D68, CVA6, CVA10, CVA16, and polioviruses (PVs), validated the 95% threshold for typing, with a few exceptions such as PV1-PV2 and CVA6-CVA10, as well as some EV-C types. This study proposes a criterion for typing based on VP4-pVP2 amino acids, which can aid in rapid enterovirus diagnosis during routine clinical or environmental surveillance and emergency outbreaks. Our research confirms the reliability of the suggested VP4-pVP2-based threshold for typing and its potential application in laboratory settings.
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Affiliation(s)
- Kouichi Kitamura
- Department of Virology II, National Institute of Infectious Diseases, Musashi-murayama, Tokyo, Japan
| | - Minetaro Arita
- Department of Virology II, National Institute of Infectious Diseases, Musashi-murayama, Tokyo, Japan
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Morobe JM, Kamau E, Luka MM, Murunga N, Lewa C, Mutunga M, Bigogo G, Otieno N, Nyawanda B, Onyango C, Nokes DJ, Agoti CN, Munywoki PK. Spatio-temporal distribution of rhinovirus types in Kenya: a retrospective analysis, 2014. Sci Rep 2024; 14:22298. [PMID: 39333386 PMCID: PMC11436855 DOI: 10.1038/s41598-024-73856-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 09/20/2024] [Indexed: 09/29/2024] Open
Abstract
The epidemiology and circulation patterns of various rhinovirus types within populations remains under-explored. We generated 803 VP4/VP2 gene sequences from rhinovirus-positive samples collected from acute respiratory illness (ARI) patients, including both in-patient and outpatient cases, between 1st January and 31st December 2014 from eleven surveillance sites across Kenya and used phylogenetics to characterise virus introductions and spread. RVs were detected throughout the year, with the highest detection rates observed from January to March and June to July. We detected a total of 114 of the 169 currently classified types. Our analysis revealed numerous virus introductions into Kenya characterized by local expansion and extinction, and extensive spatial mixing of types within the country due to the widespread transmission of the virus after an introduction. This work demonstrates that in a single year, the circulation of rhinovirus in Kenya was characterized by substantial genetic diversity, multiple introductions, and extensive geographical spread.
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Affiliation(s)
- John Mwita Morobe
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, Kilifi, Kenya.
| | - Everlyn Kamau
- Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Martha M Luka
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, Kilifi, Kenya
| | - Nickson Murunga
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, Kilifi, Kenya
| | - Clement Lewa
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, Kilifi, Kenya
| | - Martin Mutunga
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, Kilifi, Kenya
| | | | - Nancy Otieno
- KEMRI- Centre for Global Health Research, Kisumu, Kenya
| | | | - Clayton Onyango
- Division of Global Health Protection, U.S Centers for Disease Control and Prevention (CDC), Centers for Global Health, Nairobi, Kenya
| | - D James Nokes
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, Kilifi, Kenya
- School of Life Sciences, Zeeman Institute for Systems Biology and Infectious Disease Epidemiology Research (SBIDER), University of Warwick, Coventry, UK
| | - Charles N Agoti
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, Kilifi, Kenya
- Department of Public Health, Pwani University, Kilifi, Kenya
| | - Patrick K Munywoki
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, Kilifi, Kenya
- Division of Global Health Protection, U.S Centers for Disease Control and Prevention (CDC), Centers for Global Health, Nairobi, Kenya
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Vera JM, McIlwain SJ, Fye S, Palmenberg A, Bochkov YA, Li H, Pinapati R, Tan JC, Gern JE, Seroogy CM, Ong IM. Assessing immune factors in maternal milk and paired infant plasma antibody binding to human rhinoviruses. Front Immunol 2024; 15:1385121. [PMID: 39119337 PMCID: PMC11306134 DOI: 10.3389/fimmu.2024.1385121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Accepted: 05/17/2024] [Indexed: 08/10/2024] Open
Abstract
Introduction Before they can produce their own antibodies, newborns are protected from infections by transplacental transfer of maternal IgG antibodies and after birth through breast milk IgA antibodies. Rhinovirus (RV) infections are extremely common in early childhood, and while RV infections often result in only mild upper respiratory illnesses, they can also cause severe lower respiratory illnesses such as bronchiolitis and pneumonia. Methods We used high-density peptide arrays to profile infant and maternal antibody reactivity to capsid and full proteome sequences of three human RVs - A16, B52, and C11. Results Numerous plasma IgG and breast milk IgA RV epitopes were identified that localized to regions of the RV capsid surface and interior, and also to several non-structural proteins. While most epitopes were bound by both IgG and IgA, there were several instances where isotype-specific and RV-specific binding were observed. We also profiled 62 unique RV-C protein loop sequences characteristic of this species' capsid VP1 protein. Discussion Many of the RV-C loop sequences were highly bound by IgG from one-year-old infants, indicating recent or ongoing active infections, or alternatively, a level of cross-reactivity among homologous RV-C sites.
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Affiliation(s)
- Jessica M. Vera
- Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, United States
- University of Wisconsin Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, WI, United States
| | - Sean J. McIlwain
- Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, United States
- University of Wisconsin Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, WI, United States
| | - Samantha Fye
- Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, United States
| | - Ann Palmenberg
- Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, United States
| | - Yury A. Bochkov
- Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, United States
| | - Hanying Li
- Roche Nimblegen, Roche Sequencing Solutions, Madison, WI, United States
| | - Richard Pinapati
- Roche Nimblegen, Roche Sequencing Solutions, Madison, WI, United States
| | - John C. Tan
- Roche Nimblegen, Roche Sequencing Solutions, Madison, WI, United States
| | - James E. Gern
- Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, United States
| | - Christine M. Seroogy
- Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, United States
| | - Irene M. Ong
- Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, United States
- University of Wisconsin Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, WI, United States
- Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, WI, United States
- Center for Human Genomics and Precision Medicine, University of Wisconsin-Madison, Madison, WI, United States
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Mogotsi MT, Ogunbayo AE, O’Neill HG, Nyaga MM. High Detection Frequency of Vaccine-Associated Polioviruses and Non-Polio Enteroviruses in the Stools of Asymptomatic Infants from the Free State Province, South Africa. Microorganisms 2024; 12:920. [PMID: 38792747 PMCID: PMC11124149 DOI: 10.3390/microorganisms12050920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 04/24/2024] [Accepted: 04/25/2024] [Indexed: 05/26/2024] Open
Abstract
Enterovirus (EV) infections are widespread and associated with a range of clinical conditions, from encephalitis to meningitis, gastroenteritis, and acute flaccid paralysis. Knowledge about the circulation of EVs in neonatal age and early infancy is scarce, especially in Africa. This study aimed to unveil the frequency and diversity of EVs circulating in apparently healthy newborns from the Free State Province, South Africa (SA). For this purpose, longitudinally collected faecal specimens (May 2021-February 2022) from a cohort of 17 asymptomatic infants were analysed using metagenomic next-generation sequencing. Overall, seven different non-polio EV (NPEV) subtypes belonging to EV-B and EV-C species were identified, while viruses classified under EV-A and EV-D species could not be characterised at the sub-species level. Additionally, under EV-C species, two vaccine-related poliovirus subtypes (PV1 and PV3) were identified. The most prevalent NPEV species was EV-B (16/17, 94.1%), followed by EV-A (3/17, 17.6%), and EV-D (4/17, 23.5%). Within EV-B, the commonly identified NPEV types included echoviruses 6, 13, 15, and 19 (E6, E13, E15, and E19), and coxsackievirus B2 (CVB2), whereas enterovirus C99 (EV-C99) and coxsackievirus A19 (CVA19) were the only two NPEVs identified under EV-C species. Sabin PV1 and PV3 strains were predominantly detected during the first week of birth and 6-8 week time points, respectively, corresponding with the OPV vaccination schedule in South Africa. A total of 11 complete/near-complete genomes were identified from seven NPEV subtypes, and phylogenetic analysis of the three EV-C99 identified revealed that our strains were closely related to other strains from Cameroon and Brazil, suggesting global distribution of these strains. This study provides an insight into the frequency and diversity of EVs circulating in asymptomatic infants from the Free State Province, with the predominance of subtypes from EV-B and EV-C species. This data will be helpful to researchers looking into strategies for the control and treatment of EV infection.
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Affiliation(s)
- Milton T. Mogotsi
- Next Generation Sequencing Unit and Division of Virology, Faculty of Health Sciences, University of the Free State, Bloemfontein 9300, South Africa; (M.T.M.); (A.E.O.)
| | - Ayodeji E. Ogunbayo
- Next Generation Sequencing Unit and Division of Virology, Faculty of Health Sciences, University of the Free State, Bloemfontein 9300, South Africa; (M.T.M.); (A.E.O.)
| | - Hester G. O’Neill
- Department of Microbiology and Biochemistry, Faculty of Natural and Agricultural Sciences, University of the Free State, Bloemfontein 9300, South Africa;
| | - Martin M. Nyaga
- Next Generation Sequencing Unit and Division of Virology, Faculty of Health Sciences, University of the Free State, Bloemfontein 9300, South Africa; (M.T.M.); (A.E.O.)
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Berginc N, Sočan M, Prosenc Trilar K, Petrovec M. Seasonality and Genotype Diversity of Human Rhinoviruses during an Eight-Year Period in Slovenia. Microorganisms 2024; 12:341. [PMID: 38399745 PMCID: PMC10893136 DOI: 10.3390/microorganisms12020341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 01/31/2024] [Accepted: 02/02/2024] [Indexed: 02/25/2024] Open
Abstract
Due to the high socioeconomic burden of rhinoviruses, the development of prevention and treatment strategies is of high importance. Understanding the epidemiological and clinical features of rhinoviruses is essential in order to address these issues. Our study aimed to define the seasonality and molecular epidemiology of rhinoviruses in Slovenia. Over a period of eight years, a total of 20,425 patients from sentinel primary healthcare settings and sentinel hospitals were examined for a panel of respiratory viruses in the national programme for the surveillance of influenza-like illnesses and acute respiratory infections. The patients were from all age groups and had respiratory infections of various severity. Infection with a rhinovirus was confirmed using an RT-rPCR in 1834 patients, and 1480 rhinoviruses were genotyped. The molecular analysis was linked to demographical and meteorological data. We confirmed the year-round circulation of rhinoviruses with clear seasonal cycles, resulting in two seasonal waves with peaks in spring and autumn. High levels of genotype variability and co-circulation were confirmed between and within seasons and were analysed in terms of patient age, the patient source reflecting disease severity, and meteorological factors. Our study provides missing scientific information on the genotype diversity of rhinoviruses in Slovenia. As most previous investigations focused on exclusive segments of the population, such as children or hospitalised patients, and for shorter study periods, our study, with its design, size and length, contributes complementary aspects and new evidence-based knowledge to the regional and global understanding of rhinovirus seasonality and molecular epidemiology.
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Affiliation(s)
- Nataša Berginc
- Department of Public Health Microbiology, National Laboratory of Health, Environment and Food, 1000 Ljubljana, Slovenia;
| | - Maja Sočan
- Centre for Infectious Diseases, National Institute of Public Health, 1000 Ljubljana, Slovenia
| | - Katarina Prosenc Trilar
- Department of Public Health Microbiology, National Laboratory of Health, Environment and Food, 1000 Ljubljana, Slovenia;
| | - Miroslav Petrovec
- Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
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Vera JM, McIlwain SJ, Fye S, Palmenberg A, Bochkov Y, Li H, Pinapati R, Tan J, Gern JE, Seroogy C, Ong IM. Assessing Immune Factors in Maternal Milk and Paired Infant Plasma Antibody Binding to Human Rhinoviruses. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.12.17.565204. [PMID: 38187517 PMCID: PMC10769182 DOI: 10.1101/2023.12.17.565204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/09/2024]
Abstract
Before they can produce their own antibodies, newborns are protected from infections by transplacental transfer of maternal IgG antibodies and after birth through breast milk IgA antibodies. Rhinovirus (RV) infections are extremely common in early childhood, and while RV infections often result in only mild upper respiratory illnesses, they can also cause severe lower respiratory illnesses such as bronchiolitis and pneumonia. We used high-density peptide arrays to profile infant and maternal antibody reactivity to capsid and full proteome sequences of three human RVs - A16, B52, and C11. Numerous plasma IgG and breast milk IgA RV epitopes were identified that localized to regions of the RV capsid surface and interior, and also to several non-structural proteins. While most epitopes were bound by both IgG and IgA, there were several instances where isotype-specific and RV-specific binding were observed. We also profiled 62 unique RV-C dominant protein loop sequences characteristic of this species' capsid VP1 protein. Many of these RV-C sites were highly bound by IgG from one-year-old infants, indicating recent or ongoing active infections, or alternatively, a level of cross-reactivity among homologous RV-C sites.
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Ju DU, Park D, Kim IH, Kim S, Yoo HM. Development of Human Rhinovirus RNA Reference Material Using Digital PCR. Genes (Basel) 2023; 14:2210. [PMID: 38137032 PMCID: PMC10742479 DOI: 10.3390/genes14122210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 12/08/2023] [Accepted: 12/11/2023] [Indexed: 12/24/2023] Open
Abstract
The human rhinovirus (RV) is a positive-stranded RNA virus that causes respiratory tract diseases affecting both the upper and lower halves of the respiratory system. RV enhances its replication by concentrating RNA synthesis within a modified host membrane in an intracellular compartment. RV infections often occur alongside infections caused by other respiratory viruses, and the RV virus may remain asymptomatic for extended periods. Alongside qualitative detection, it is essential to accurately quantify RV RNA from clinical samples to explore the relationships between RV viral load, infections caused by the virus, and the resulting symptoms observed in patients. A reference material (RM) is required for quality evaluation, the performance evaluation of molecular diagnostic products, and evaluation of antiviral agents in the laboratory. The preparation process for the RM involves creating an RV RNA mixture by combining RV viral RNA with RNA storage solution and matrix. The resulting RV RNA mixture is scaled up to a volume of 25 mL, then dispensed at 100 µL per vial and stored at -80 °C. The process of measuring the stability and homogeneity of RV RMs was conducted by employing reverse transcription droplet digital polymerase chain reaction (RT-ddPCR). Digital PCR is useful for the analysis of standards and can help to improve measurement compatibility: it represents the equivalence of a series of outcomes for reference materials and samples being analyzed when a few measurement procedures are employed, enabling objective comparisons between quantitative findings obtained through various experiments. The number of copies value represents a measured result of approximately 1.6 × 105 copies/μL. The RM has about an 11% bottle-to-bottle homogeneity and shows stable results for 1 week at temperatures of 4 °C and -20 °C and for 12 months at a temperature of -80 °C. The developed RM can enhance the dependability of RV molecular tests by providing a precise reference value for the absolute copy number of a viral target gene. Additionally, it can serve as a reference for diverse studies.
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Affiliation(s)
- Dong U Ju
- Biometrology Group, Korea Research Institute of Standards and Science (KRISS), Daejeon 34113, Republic of Korea
- School of Biomedical Engineering, Korea University, Seoul 02841, Republic of Korea
| | - Dongju Park
- Biometrology Group, Korea Research Institute of Standards and Science (KRISS), Daejeon 34113, Republic of Korea
| | - Il-Hwan Kim
- Biometrology Group, Korea Research Institute of Standards and Science (KRISS), Daejeon 34113, Republic of Korea
| | - Seil Kim
- Biometrology Group, Korea Research Institute of Standards and Science (KRISS), Daejeon 34113, Republic of Korea
- Department of Precision Measurement, University of Science & Technology (UST), Daejeon 34113, Republic of Korea
| | - Hee Min Yoo
- Biometrology Group, Korea Research Institute of Standards and Science (KRISS), Daejeon 34113, Republic of Korea
- Department of Precision Measurement, University of Science & Technology (UST), Daejeon 34113, Republic of Korea
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Zhao P, Shao N, Dong J, Su H, Sui H, Zhang T, Yang F. Genetic diversity and characterization of rhinoviruses from Chinese clinical samples with a global perspective. Microbiol Spectr 2023; 11:e0084023. [PMID: 37733296 PMCID: PMC10715137 DOI: 10.1128/spectrum.00840-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Accepted: 08/03/2023] [Indexed: 09/22/2023] Open
Abstract
IMPORTANCE Based on clinical samples collected in China, we detected and reported 22 types for the first time in China, as well as three types for the first time in Asia, and reported their genetic characteristics and diversity. We identified a novel type of Rhinovirus (RV), A110, highlighting its unique genetic features. We annotated the genomic structure and serotype of all the existing RV sequences in the database, and four novel RV types were identified and their genetic diversity reported. Combined with the sequence annotation, we constructed a complete VP1 data set of RV and conducted the first large-scale evolutionary dynamics analysis of RV. Based on a high-quality data set, we conducted a comprehensive analysis of the guanine-cytosine (GC) content variations among serotypes of RVs. This study provides crucial theoretical support and valuable data for understanding RV's genetic diversity and developing antiviral strategies.
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Affiliation(s)
- Peng Zhao
- NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Nan Shao
- NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jie Dong
- NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Haoxiang Su
- NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hongtao Sui
- NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ting Zhang
- NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fan Yang
- NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences, Beijing, China
- State Key Laboratory of Respiratory Health and Multimorbidity, Beijing, China
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Luka MM, Otieno JR, Kamau E, Morobe JM, Murunga N, Adema I, Nyiro JU, Macharia PM, Bigogo G, Otieno NA, Nyawanda BO, Rabaa MA, Emukule GO, Onyango C, Munywoki PK, Agoti CN, Nokes DJ. Rhinovirus dynamics across different social structures. NPJ VIRUSES 2023; 1:6. [PMID: 38665239 PMCID: PMC11041716 DOI: 10.1038/s44298-023-00008-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Accepted: 10/30/2023] [Indexed: 04/28/2024]
Abstract
Rhinoviruses (RV), common human respiratory viruses, exhibit significant antigenic diversity, yet their dynamics across distinct social structures remain poorly understood. Our study delves into RV dynamics within Kenya by analysing VP4/2 sequences across four different social structures: households, a public primary school, outpatient clinics in the Kilifi Health and Demographics Surveillance System (HDSS), and countrywide hospital admissions and outpatients. The study revealed the greatest diversity of RV infections at the countrywide level (114 types), followed by the Kilifi HDSS (78 types), the school (47 types), and households (40 types), cumulatively representing >90% of all known RV types. Notably, RV diversity correlated directly with the size of the population under observation, and several RV type variants occasionally fuelled RV infection waves. Our findings highlight the critical role of social structures in shaping RV dynamics, information that can be leveraged to enhance public health strategies. Future research should incorporate whole-genome analysis to understand fine-scale evolution across various social structures.
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Affiliation(s)
- Martha M. Luka
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research – Coast, Kilifi, Kenya
- Department of Biochemistry and Biotechnology, Pwani University, Kilifi, Kenya
- Present Address: School of Biodiversity, One Health and Veterinary Medicine, University of Glasgow, Glasgow, G12 8QQ UK
| | - James R. Otieno
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research – Coast, Kilifi, Kenya
| | - Everlyn Kamau
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research – Coast, Kilifi, Kenya
| | - John Mwita Morobe
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research – Coast, Kilifi, Kenya
| | - Nickson Murunga
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research – Coast, Kilifi, Kenya
| | - Irene Adema
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research – Coast, Kilifi, Kenya
| | - Joyce Uchi Nyiro
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research – Coast, Kilifi, Kenya
| | - Peter M. Macharia
- Population & Health Impact Surveillance Group, KEMRI-Wellcome Trust Research Programme, Nairobi, Kenya
- Centre for Health Informatics, Computing, and Statistics, Lancaster Medical School, Lancaster University, Lancaster, UK
- Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium
| | | | | | | | - Maia A. Rabaa
- Coronavirus and Other Respiratory Viruses Division (CORVD), National Center for Immunization and Respiratory Diseases (NCIRD), U.S. Centers of Disease Control and Prevention (CDC), Atlanta, GA USA
| | - Gideon O. Emukule
- U.S. Centers of Disease Control and Prevention (CDC), Nairobi, Kenya
| | - Clayton Onyango
- U.S. Centers of Disease Control and Prevention (CDC), Nairobi, Kenya
| | - Patrick K. Munywoki
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research – Coast, Kilifi, Kenya
- U.S. Centers of Disease Control and Prevention (CDC), Nairobi, Kenya
| | - Charles N. Agoti
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research – Coast, Kilifi, Kenya
- Department of Public Health, Pwani University, Kilifi, Kenya
| | - D. James Nokes
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research – Coast, Kilifi, Kenya
- School of Life Sciences and Zeeman Institute for Systems Biology and Infectious Disease Epidemiology Research (SBIDER), University of Warwick, Coventry, UK
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Strochkov V, Beloussov V, Solomadin M, Granica J, Yegorov S, Orkara S, Sandybayev N. Full genome sequence of a human rhinovirus A1B, obtained in Kazakhstan. Microbiol Resour Announc 2023; 12:e0074923. [PMID: 37796012 PMCID: PMC10652953 DOI: 10.1128/mra.00749-23] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Accepted: 08/30/2023] [Indexed: 10/06/2023] Open
Abstract
Here, we report the full nucleotide sequence of the RvA1B/KZ/2021/87 rhinovirus, identified through metagenomic sequencing of nasopharyngeal swabs collected from patients exhibiting respiratory symptoms in Kazakhstan during 2021.
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Affiliation(s)
- Vitaliy Strochkov
- Kazakhstan-Japan Innovation Centre, Kazakh National Agrarian Research University (KazNARU), Almaty, Kazakhstan
| | | | - Maxim Solomadin
- School of Pharmacy, Karaganda Medical University, Karaganda, Kazakhstan
| | - Joanna Granica
- TreeGene Molecular Genetics Laboratory, Almaty, Kazakhstan
| | - Sergey Yegorov
- Department of Biochemistry and Biomedical Sciences, Michael G. DeGroote Institute for Infectious Disease Research, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada
- School of Sciences and Humanities, Nazarbayev University, Astana, Kazakhstan
| | - Shynggys Orkara
- Kazakhstan-Japan Innovation Centre, Kazakh National Agrarian Research University (KazNARU), Almaty, Kazakhstan
| | - Nurlan Sandybayev
- Kazakhstan-Japan Innovation Centre, Kazakh National Agrarian Research University (KazNARU), Almaty, Kazakhstan
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Georgieva I, Stoyanova A, Angelova S, Korsun N, Stoitsova S, Nikolaeva-Glomb L. Rhinovirus Genotypes Circulating in Bulgaria, 2018-2021. Viruses 2023; 15:1608. [PMID: 37515294 PMCID: PMC10385483 DOI: 10.3390/v15071608] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/19/2023] [Accepted: 07/20/2023] [Indexed: 07/30/2023] Open
Abstract
Rhinoviruses (RV) are one of the most common causative agents of respiratory infections, with significant socioeconomic impact. RV infections are not notifiable in Bulgaria, and little is known about the different RV genotypes circulating in the country. This study aims to investigate the diversity of RV genotypes that were circulating in Bulgaria in the period 2018-2021 in samples from ILI/ARI patients. Genotype assignment was based on sequencing and phylogenetic analysis of the 5' untranslated region and the VP4-VP2 region. Out of a total of 1385 nasopharyngeal swabs tested, 166 were RV-positive (RV detection rate: 11.99% (166/1385)). Those with a cycle threshold <25 were selected for genotyping (n = 63). RV isolates were successfully genotyped and classified into 34 genotypes within Rhinovirus A (RV-A), Rhinovirus B (RV-B) and Rhinovirus C (RV-C) species. Presumptive recombination events between the 5'UTR and VP4-VP2 regions were detected in three of the isolates. RV-A and RV-C were the prevalent RV species, with significantly more frequent detections of RV-A in the years before the COVID-19 pandemic compared to the post-pandemic period, when RV-C prevailed. The present study is the first to determine RV genotypes in Bulgaria and the circulation of RV-C has been described for the first time in the country.
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Affiliation(s)
- Irina Georgieva
- Department of Virology, National Centre of Infectious and Parasitic Diseases, 1233 Sofia, Bulgaria
| | - Asya Stoyanova
- Department of Virology, National Centre of Infectious and Parasitic Diseases, 1233 Sofia, Bulgaria
| | - Svetla Angelova
- Clinic of Infectious Diseases, University Hospital "Prof. Dr. Stoyan Kirkovich" AD, 6003 Stara Zagora, Bulgaria
| | - Neli Korsun
- Department of Virology, National Centre of Infectious and Parasitic Diseases, 1233 Sofia, Bulgaria
| | - Savina Stoitsova
- Department of Virology, National Centre of Infectious and Parasitic Diseases, 1233 Sofia, Bulgaria
| | - Lubomira Nikolaeva-Glomb
- Department of Virology, National Centre of Infectious and Parasitic Diseases, 1233 Sofia, Bulgaria
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12
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Alsayed AR, Abed A, Abu-Samak M, Alshammari F, Alshammari B. Etiologies of Acute Bronchiolitis in Children at Risk for Asthma, with Emphasis on the Human Rhinovirus Genotyping Protocol. J Clin Med 2023; 12:3909. [PMID: 37373604 DOI: 10.3390/jcm12123909] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 05/22/2023] [Accepted: 05/26/2023] [Indexed: 06/29/2023] Open
Abstract
This research aims to determine acute bronchiolitis' causative virus(es) and establish a viable protocol to classify the Human Rhinovirus (HRV) species. During 2021-2022, we included children 1-24 months of age with acute bronchiolitis at risk for asthma. The nasopharyngeal samples were taken and subjected to a quantitative polymerase chain reaction (qPCR) in a viral panel. For HRV-positive samples, a high-throughput assay was applied, directing the VP4/VP2 and VP3/VP1 regions to confirm species. BLAST searching, phylogenetic analysis, and sequence divergence took place to identify the degree to which these regions were appropriate for identifying and differentiating HRV. HRV ranked second, following RSV, as the etiology of acute bronchiolitis in children. The conclusion of the investigation of all available data in this study distributed sequences into 7 HRV-A, 1 HRV-B, and 7 HRV-C types based on the VP4/VP2 and VP3/VP1 sequences. The nucleotide divergence between the clinical samples and the corresponding reference strains was lower in the VP4/VP2 region than in the VP3/VP1 region. The results demonstrated the potential utility of the VP4/VP2 region and the VP3/VP1 region for differentiating HRV genotypes. Confirmatory outcomes were yielded, indicating how nested and semi-nested PCR can establish practical ways to facilitate HRV sequencing and genotyping.
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Affiliation(s)
- Ahmad R Alsayed
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan
| | - Anas Abed
- Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 11931, Jordan
| | - Mahmoud Abu-Samak
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan
| | - Farhan Alshammari
- Department of Pharmaceutics, College of Pharmacy, University of Hail, Hail 2440, Saudi Arabia
| | - Bushra Alshammari
- Department of Medical Surgical Nursing, College of Nursing, University of Hail, Hail 2440, Saudi Arabia
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13
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Zhang Q, Xie Z, Xia B, Wang Y, Xu W, Zhang Y. Identification of two proposed novel human rhinovirus types: Bpat107 and Cpat58. J Med Virol 2023; 95:e28531. [PMID: 36698256 DOI: 10.1002/jmv.28531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 12/30/2022] [Accepted: 01/24/2023] [Indexed: 01/27/2023]
Abstract
Human rhinovirus (RV) is an important viral pathogen associated with severe acute respiratory tract infection. The present study retrospectively identified RV types in hospitalized patients with severe acute respiratory infection (SARI) from October 2017 to June 2019 in Henan Province, China. Real-time PCR was used to screen pharyngeal swab samples for RV. Then, the VP1 gene sequences of RV-positive samples were amplified and sequenced with nested primer PCR; subsequently, analyses of the molecular epidemiology and genetic diversity characteristics of the RV types were performed. Seventy-three out of 1015 respiratory samples were identified as RV-positive, from which 65 complete VP1 sequences were successfully sequenced. These RVs were classified into 41 different types, including 26 RV-A types, 2 RV-B types, and 13 RV-C types. The RVs showed an obvious seasonal distribution, with peaks in summer and autumn. The epidemic peak of RV-C was later than that of RV-A. In addition, two new types of species, B and C, were proposed, Bpat107 and Cpat58, respectively. Compared with other types in the same RV species, the pairwise nucleotide p-distances of the two novel RV types were 0.262~0.402 and 0.251~0.508, respectively. This study analyzed the seasonal and genetic characteristics of RV associated with SARI cases in Henan Province, China. Two novel RV types were proposed.
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Affiliation(s)
- Qiang Zhang
- NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Zhibo Xie
- NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Baicheng Xia
- NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Yage Wang
- NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Wenbo Xu
- NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.,Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China
| | - Yan Zhang
- NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.,Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China
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14
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Wu X, Cui L, Bai Y, Bian L, Liang Z. Pseudotyped Viruses for Enterovirus. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1407:209-228. [PMID: 36920699 DOI: 10.1007/978-981-99-0113-5_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
Using a non-pathogenic pseudotyped virus as a surrogate for a wide-type virus in scientific research complies with the recent requirements for biosafety. Enterovirus (EV) contains many species of viruses, which are a type of nonenveloped virus. The preparation of its corresponding pseudotyped virus often needs customized construction compared to some enveloped viruses. This article describes the procedures and challenges in the construction of pseudotyped virus for enterovirus (pseudotyped enterovirus, EVpv) and also introduces the application of EVpv in basic virological research, serological monitoring, and the detection of neutralizing antibody (NtAb).
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Affiliation(s)
- Xing Wu
- Division of Hepatitis Virus & Enterovirus Vaccines, Institute for Biological Products, National Institutes for Food and Drug Control, Beijing, China
- WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, China
| | - Lisha Cui
- Minhai biotechnology Co. Ltd, Beijing, China
| | - Yu Bai
- Division of Hepatitis Virus & Enterovirus Vaccines, Institute for Biological Products, National Institutes for Food and Drug Control, Beijing, China
- WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, China
| | - Lianlian Bian
- Division of Hepatitis Virus & Enterovirus Vaccines, Institute for Biological Products, National Institutes for Food and Drug Control, Beijing, China
- WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, China
| | - Zhenglun Liang
- Division of Hepatitis Virus & Enterovirus Vaccines, Institute for Biological Products, National Institutes for Food and Drug Control, Beijing, China
- WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, China
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15
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Esneau C, Duff AC, Bartlett NW. Understanding Rhinovirus Circulation and Impact on Illness. Viruses 2022; 14:141. [PMID: 35062345 PMCID: PMC8778310 DOI: 10.3390/v14010141] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 01/08/2022] [Accepted: 01/10/2022] [Indexed: 01/27/2023] Open
Abstract
Rhinoviruses (RVs) have been reported as one of the main viral causes for severe respiratory illnesses that may require hospitalization, competing with the burden of other respiratory viruses such as influenza and RSV in terms of severity, economic cost, and resource utilization. With three species and 169 subtypes, RV presents the greatest diversity within the Enterovirus genus, and despite the efforts of the research community to identify clinically relevant subtypes to target therapeutic strategies, the role of species and subtype in the clinical outcomes of RV infection remains unclear. This review aims to collect and organize data relevant to RV illness in order to find patterns and links with species and/or subtype, with a specific focus on species and subtype diversity in clinical studies typing of respiratory samples.
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Affiliation(s)
| | | | - Nathan W. Bartlett
- Hunter Medical Research Institute, College of Health Medicine and Wellbeing, University of Newcastle, New Lambton Heights, NSW 2305, Australia; (C.E.); (A.C.D.)
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16
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Mikkola H, Honkila M, Tapiainen T, Jartti T. Susceptibility to rhinovirus-induced early wheezing as a risk factor for subsequent asthma development. CURRENT RESPIRATORY MEDICINE REVIEWS 2022. [DOI: 10.2174/1573398x18666220103113813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Abstract:
Rhinovirus is one of the two most common viral agents that cause bronchiolitis in young children. During the first 12 months, it is second to the respiratory syncytial virus, but after 12 months, it begins dominating the statistics. Wheezing and dry cough are typical clinical symptoms indicative of rhinovirus-induced bronchiolitis, although overlap of symptoms with other virus infections is common. Several studies have shown that atopic predisposition and reduced interferon responses increase susceptibility to rhinovirus-induced wheezing. More recent studies have found that certain genetic variations at strong asthma loci also increase susceptibility. Rhinovirus-induced wheezing in the early years of life is known to increase the risk of subsequent asthma development and may be associated with airway remodeling. This risk is increased by aeroallergen sensitization. Currently, there are no clinically approved preventive treatments for asthma. However, studies show promising results indicating that children with rhinovirus-affected first-time wheezing respond to bronchodilators in terms of less short-term symptoms and that controlling airway inflammatory responses with anti-inflammatory medication may markedly decrease asthma development. Also, enhancing resistance to respiratory viruses has been a topic of discussion. Primary and secondary prevention strategies are being developed with the aim of decreasing the incidence of asthma. Here, we review the current knowledge on rhinovirus-induced early wheezing as a risk factor for subsequent asthma development and related asthma-prevention strategies.
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Affiliation(s)
- Hannele Mikkola
- PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu, Oulu, Finland
| | - Minna Honkila
- PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu, Oulu, Finland
- Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland
| | - Terhi Tapiainen
- PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu, Oulu, Finland
- Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland
| | - Tuomas Jartti
- PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu, Oulu, Finland
- Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland
- Department of Pediatrics and Adolescent Medicine, University of Turku and Turku University Hospital, Turku, Finland
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17
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Gagliardi TB, Goldstein ME, Song D, Gray KM, Jung JW, Ignacio MA, Stroka KM, Duncan GA, Scull MA. Rhinovirus C replication is associated with the endoplasmic reticulum and triggers cytopathic effects in an in vitro model of human airway epithelium. PLoS Pathog 2022; 18:e1010159. [PMID: 34995322 PMCID: PMC8741012 DOI: 10.1371/journal.ppat.1010159] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 11/29/2021] [Indexed: 12/21/2022] Open
Abstract
The clinical impact of rhinovirus C (RV-C) is well-documented; yet, the viral life cycle remains poorly defined. Thus, we characterized RV-C15 replication at the single-cell level and its impact on the human airway epithelium (HAE) using a physiologically-relevant in vitro model. RV-C15 replication was restricted to ciliated cells where viral RNA levels peaked at 12 hours post-infection (hpi), correlating with elevated titers in the apical compartment at 24hpi. Notably, infection was associated with a loss of polarized expression of the RV-C receptor, cadherin-related family member 3. Visualization of double-stranded RNA (dsRNA) during RV-C15 replication revealed two distinct replication complex arrangements within the cell, likely corresponding to different time points in infection. To further define RV-C15 replication sites, we analyzed the expression and colocalization of giantin, phosphatidylinositol-4-phosphate, and calnexin with dsRNA. Despite observing Golgi fragmentation by immunofluorescence during RV-C15 infection as previously reported for other RVs, a high ratio of calnexin-dsRNA colocalization implicated the endoplasmic reticulum as the primary site for RV-C15 replication in HAE. RV-C15 infection was also associated with elevated stimulator of interferon genes (STING) expression and the induction of incomplete autophagy, a mechanism used by other RVs to facilitate non-lytic release of progeny virions. Notably, genetic depletion of STING in HAE attenuated RV-C15 and -A16 (but not -B14) replication, corroborating a previously proposed proviral role for STING in some RV infections. Finally, RV-C15 infection resulted in a temporary loss in epithelial barrier integrity and the translocation of tight junction proteins while a reduction in mucociliary clearance indicated cytopathic effects on epithelial function. Together, our findings identify both shared and unique features of RV-C replication compared to related rhinoviruses and define the impact of RV-C on both epithelial cell organization and tissue functionality–aspects of infection that may contribute to pathogenesis in vivo. Rhinovirus C has a global distribution and significant clinical impact–especially in those with underlying lung disease. Although RV-C is genetically, structurally, and biologically distinct from RV-A and -B viruses, our understanding of the RV-C life cycle has been largely inferred from these and other related viruses. Here, we performed a detailed analysis of RV-C15 replication in a physiologically-relevant model of human airway epithelium. Our single-cell, microscopy-based approach revealed that–unlike other RVs–the endoplasmic reticulum is the primary site for RV-C15 replication. RV-C15 replication also stimulated STING expression, which was proviral, and triggered dramatic changes in cellular organization, including altered virus receptor distribution, fragmented Golgi stacks, and the induction of incomplete autophagy. Additionally, we observed a loss of epithelial barrier function and a decrease in mucociliary clearance, a major defense mechanism in the lung, during RV-C15 infection. Together, these data reveal novel insight into RV-C15 replication dynamics and resulting cytopathic effects in the primary target cells for infection, thereby furthering our understanding of the pathogenesis of RV-C. Our work highlights similar, as well as unique, aspects of RV-C15 replication compared to related pathogens, which will help guide future studies on the molecular mechanisms of RV-C infection.
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Affiliation(s)
- Talita B. Gagliardi
- Department of Cell Biology and Molecular Genetics, Maryland Pathogen Research Institute, University of Maryland, College Park, Maryland, United States of America
| | - Monty E. Goldstein
- Department of Cell Biology and Molecular Genetics, Maryland Pathogen Research Institute, University of Maryland, College Park, Maryland, United States of America
| | - Daniel Song
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, United States of America
| | - Kelsey M. Gray
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, United States of America
| | - Jae W. Jung
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, United States of America
| | - Maxinne A. Ignacio
- Department of Cell Biology and Molecular Genetics, Maryland Pathogen Research Institute, University of Maryland, College Park, Maryland, United States of America
| | - Kimberly M. Stroka
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, United States of America
- Biophysics Program, University of Maryland, College Park, Maryland, United States of America
- Center for Stem Cell Biology and Regenerative Medicine, University of Maryland, Baltimore, Maryland, United States of America
- Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, Maryland, United States of America
| | - Gregg A. Duncan
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, United States of America
| | - Margaret A. Scull
- Department of Cell Biology and Molecular Genetics, Maryland Pathogen Research Institute, University of Maryland, College Park, Maryland, United States of America
- * E-mail:
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18
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Morikawa S, Otsuka M, Yumisashi T, Motomura K. A longitudinal study on respiratory viral infection for healthy volunteers. Health Sci Rep 2021; 4:e413. [PMID: 34632101 PMCID: PMC8488996 DOI: 10.1002/hsr2.413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 08/30/2021] [Accepted: 09/06/2021] [Indexed: 11/30/2022] Open
Affiliation(s)
- Saeko Morikawa
- Virology Section, Division of MicrobiologyOsaka Institute of Public HealthOsakaJapan
| | - Maki Otsuka
- Virology Section, Division of MicrobiologyOsaka Institute of Public HealthOsakaJapan
- Department of Public HealthOsaka City University Graduate School of MedicineOsakaJapan
| | - Takahiro Yumisashi
- Virology Section, Division of MicrobiologyOsaka Institute of Public HealthOsakaJapan
| | - Kazushi Motomura
- Division of Public HealthOsaka Institute of Public HealthOsakaJapan
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19
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Mwita Morobe J, Kamau E, Murunga N, Gatua W, Luka MM, Lewa C, Cheruiyot R, Mutunga M, Odundo C, James Nokes D, Agoti CN. Trends and Intensity of Rhinovirus Invasions in Kilifi, Coastal Kenya, Over a 12-Year Period, 2007-2018. Open Forum Infect Dis 2021; 8:ofab571. [PMID: 34988244 PMCID: PMC8694214 DOI: 10.1093/ofid/ofab571] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 11/11/2021] [Indexed: 12/05/2022] Open
Abstract
Background Rhinoviruses (RVs) are ubiquitous pathogens and the principal etiological agents of common cold. Despite the high frequency of RV infections, data describing their long-term epidemiological patterns in a defined population remain limited. Methods Here, we analyzed 1070 VP4/VP2 genomic region sequences sampled at Kilifi County Hospital on the Kenya coast. The samples were collected between 2007 and 2018 from hospitalized pediatric patients (<60 months of age) with acute respiratory illness. Results Of 7231 children enrolled, RV was detected in 1497 (20.7%) and VP4/VP2 sequences were recovered from 1070 samples (71.5%). A total of 144 different RV types were identified (67 Rhinovirus A, 18 Rhinovirus B, and 59 Rhinovirus C) and at any month, several types co-circulated with alternating predominance. Within types, multiple genetically divergent variants were observed. Ongoing RV infections through time appeared to be a combination of (1) persistent types (observed up to 7 consecutive months), (2) reintroduced genetically distinct variants, and (3) new invasions (average of 8 new types annually). Conclusions Sustained RV presence in the Kilifi community is mainly due to frequent invasion by new types and variants rather than continuous transmission of locally established types/variants.
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Affiliation(s)
- John Mwita Morobe
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research, Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya
| | - Everlyn Kamau
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research, Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya.,Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Nickson Murunga
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research, Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya
| | - Winfred Gatua
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research, Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya
| | - Martha M Luka
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research, Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya
| | - Clement Lewa
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research, Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya
| | - Robinson Cheruiyot
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research, Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya
| | - Martin Mutunga
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research, Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya
| | - Calleb Odundo
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research, Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya
| | - D James Nokes
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research, Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya.,School of Life Sciences and Zeeman Institute for Systems Biology and Infectious Disease Epidemiology Research, University of Warwick, Coventry, United Kingdom
| | - Charles N Agoti
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research, Programme, Centre for Geographic Medicine Research-Coast, Kilifi, Kenya.,Department of Public Health, Pwani University, Kilifi, Kenya
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20
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Haddad-Boubaker S, Ben Hamda C, Ghedira K, Mefteh K, Bouafsoun A, Boutiba-Ben Boubaker I, Slim A, Menif K, Triki H, Ben Hadj Kacem MA, Smaoui H. Phylogeography and phylogeny of Rhinoviruses collected from Severe Acute Respiratory Infection (SARI) cases over successive epidemic periods in Tunisia. PLoS One 2021; 16:e0259859. [PMID: 34807924 PMCID: PMC8608298 DOI: 10.1371/journal.pone.0259859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 10/27/2021] [Indexed: 11/24/2022] Open
Abstract
Rhinoviruses (RV) are a major cause of Severe Acute Respiratory Infection (SARI) in children, with high genotypic diversity in different regions. However, RV type diversity remains unknown in several regions of the world. In this study, the genetic variability of the frequently circulating RV types in Northern Tunisia was investigated, using phylogenetic and phylogeographic analyses with a specific focus on the most frequent RV types: RV-A101 and RV-C45. This study concerned 13 RV types frequently circulating in Northern Tunisia. They were obtained from respiratory samples collected in 271 pediatric SARI cases, between September 2015 and November 2017. A total of 37 RV VP4-VP2 sequences, selected among a total of 49 generated sequences, was compared to 359 sequences from different regions of the world. Evolutionary analysis of RV-A101 and RV-C45 showed high genetic relationship between different Tunisian strains and Malaysian strains. RV-A101 and C45 progenitor viruses’ dates were estimated in 1981 and 1995, respectively. Since the early 2000s, the two types had a wide spread throughout the world. Phylogenetic analyses of other frequently circulating strains showed significant homology of Tunisian strains from the same epidemic period, in contrast with earlier strains. The genetic relatedness of RV-A101 and RV-C45 might result from an introduction of viruses from different clades followed by local dissemination rather than a local persistence of an endemic clades along seasons. International traffic may play a key role in the spread of RV-A101, RV-C45, and other RVs.
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Affiliation(s)
- Sondes Haddad-Boubaker
- Laboratory of Microbiology, Bechir Hamza Children’s Hospital, Bab-Saadoun Square, Tunis, Tunisia
- * E-mail:
| | - Cherif Ben Hamda
- Laboratory of Bioinformatics, Biomathematics and Biostatistics, Institut Pasteur de Tunis, University of Tunis El-Manar, Tunis, Tunisia
| | - Kais Ghedira
- Laboratory of Bioinformatics, Biomathematics and Biostatistics, Institut Pasteur de Tunis, University of Tunis El-Manar, Tunis, Tunisia
| | - Khaoula Mefteh
- Laboratory of Microbiology, Bechir Hamza Children’s Hospital, Bab-Saadoun Square, Tunis, Tunisia
- Microbiology of Children and Immunocompromised, Faculty of Medicine of Tunis, University of Tunis El-Manar, Tunis, Tunisia
| | - Aida Bouafsoun
- Laboratory of Microbiology, Bechir Hamza Children’s Hospital, Bab-Saadoun Square, Tunis, Tunisia
- Microbiology of Children and Immunocompromised, Faculty of Medicine of Tunis, University of Tunis El-Manar, Tunis, Tunisia
| | - Ilhem Boutiba-Ben Boubaker
- Laboratory of Microbiology, Charles Nicolle Hospital, Tunis, Tunisia
- Laboratory Research ‘‘Antimicrobial Resistance”, Faculty of Medicine of Tunis University of Tunis El-Manar, Tunis, Tunisia
| | - Amin Slim
- Laboratory of Microbiology, Charles Nicolle Hospital, Tunis, Tunisia
| | - Khaled Menif
- Pediatric Intensive Care Unit, Bechir Hamza Children’s Hospital in Tunis, Bab-Saadoun Square, Tunis Tunisia
| | | | - Mohamed Ali Ben Hadj Kacem
- Pediatric Intensive Care Unit, Bechir Hamza Children’s Hospital in Tunis, Bab-Saadoun Square, Tunis Tunisia
| | - Hanen Smaoui
- Laboratory of Microbiology, Bechir Hamza Children’s Hospital, Bab-Saadoun Square, Tunis, Tunisia
- Microbiology of Children and Immunocompromised, Faculty of Medicine of Tunis, University of Tunis El-Manar, Tunis, Tunisia
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21
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Han M, Ishikawa T, Stroupe CC, Breckenridge HA, Bentley JK, Hershenson MB. Deficient inflammasome activation permits an exaggerated asthma phenotype in rhinovirus C-infected immature mice. Mucosal Immunol 2021; 14:1369-1380. [PMID: 34354243 PMCID: PMC8542611 DOI: 10.1038/s41385-021-00436-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 07/07/2021] [Accepted: 07/15/2021] [Indexed: 02/04/2023]
Abstract
Compared to other RV species, RV-C has been associated with more severe respiratory illness and is more likely to occur in children with a history of asthma or who develop asthma. We therefore inoculated 6-day-old mice with sham, RV-A1B, or RV-C15. Inflammasome priming and activation were assessed, and selected mice treated with recombinant IL-1β. Compared to RV-A1B infection, RV-C15 infection induced an exaggerated asthma phenotype, with increased mRNA expression of Il5, Il13, Il25, Il33, Muc5ac, Muc5b, and Clca1; increased lung lineage-negative CD25+CD127+ST2+ ILC2s; increased mucous metaplasia; and increased airway responsiveness. Lung vRNA, induction of pro-inflammatory type 1 cytokines, and inflammasome priming (pro-IL-1β and NLRP3) were not different between the two viruses. However, inflammasome activation (mature IL-1β and caspase-1 p12) was reduced in RV-C15-infected mice compared to RV-A1B-infected mice. A similar deficiency was found in cultured macrophages. Finally, IL-1β treatment decreased RV-C-induced type 2 cytokine and mucus-related gene expression, ILC2s, mucous metaplasia, and airway responsiveness but not lung vRNA level. We conclude that RV-C induces an enhanced asthma phenotype in immature mice. Compared to RV-A, RV-C-induced macrophage inflammasome activation and IL-1β are deficient, permitting exaggerated type 2 inflammation and mucous metaplasia.
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Affiliation(s)
- Mingyuan Han
- Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Tomoko Ishikawa
- Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Claudia C Stroupe
- Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Haley A Breckenridge
- Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA
| | - J Kelley Bentley
- Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Marc B Hershenson
- Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA.
- Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
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Bioinformatics analysis of rhinovirus capsid proteins VP1-4 sequences for cross-serotype vaccine development. J Infect Public Health 2021; 14:1603-1611. [PMID: 34624714 DOI: 10.1016/j.jiph.2021.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Revised: 08/28/2021] [Accepted: 09/01/2021] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND Rhinoviruses (RV) are associated with the development and exacerbations of asthma and chronic obstructive pulmonary disease. They've also been linked to more severe diseases like pneumonia, acute bronchiolitis, croup, and otitis media. Because of the hypervariable sequences in the same serotypes, no effective vaccine against rhinoviruses has been developed to date. With the availability of new full-length genome sequences for all RV-A and RV-B serotyped strains, this study used bioinformatics to find a suitable RV strain with the highest similarity matrices to the other strains. METHODS The full genomic sequences of all known different RV-A and -B prototypes were downloaded from the National Centre for Biotechnology Information (NCBI) and divided into minor low-density lipoprotein receptor (LDLR) and major intercellular adhesion molecule groups (ICAM). The sequences were edited using Biological Sequence Alignment Editor, v 7.2.0 (BioEdit software) to study each capsid protein (VP1, VP2, VP3, and VP4) and analyzed using the EMBL-EBI ClustalW server and the more current Clustal Omega tool for the calculation of the identities and similarities. RESULTS We analyzed and predicted immunogenic motifs from capsid proteins that are conserved across distinct RV serotypes using a bioinformatics technique. The amino acid sequences of VP3 were found to be the most varied, while VP4 was the most conserved protein among all RV-A and RV-B strains. Among all strains studied, RV-74 demonstrated the highest degree of homology to other strains and could be a potential genetic source for recombinant protein production. Nine highly conserved regions with a minimum length of 9-mers were identified, which could serve as potential immune targets against rhinoviruses. CONCLUSION Therefore, bioinformatics analysis conducted in the current study has paved the way for the selection of immunogenic targets. Bioinformatically, the ideal strain's capsid protein is suggested to contain the most common RVs immunogenic sites.
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Zhang YM. Orosomucoid-like protein 3, rhinovirus and asthma. World J Crit Care Med 2021; 10:170-182. [PMID: 34616654 PMCID: PMC8462028 DOI: 10.5492/wjccm.v10.i5.170] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/16/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
The genetic variants of orosomucoid-like protein 3 (ORMDL3) gene are associated with highly significant increases in the number of human rhinovirus (HRV)-induced wheezing episodes in children. Recent investigations have been focused on the mechanisms of ORMDL3 in rhinovirus infection for asthma and asthma exacerbations. ORMDL3 not only regulates major human rhinovirus receptor intercellular adhesion molecule 1 expression, but also plays pivotal roles in viral infection through metabolisms of ceramide and sphingosine-1-phosphate, endoplasmic reticulum (ER) stress, ER-Golgi interface and glycolysis. Research on the roles of ORMDL3 in HRV infection will lead us to identify new biomarkers and novel therapeutic targets in childhood asthma and viral induced asthma exacerbations.
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Affiliation(s)
- You-Ming Zhang
- Section of Genomic and Environmental Medicine, National Heart and Lung Institute, Molecular Genetics Group, Division of Respiratory Sciences, Imperial College London, London SW3 6LY, United Kingdom
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24
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Lu L, Ashworth J, Nguyen D, Li K, Smith DB, Woolhouse M. No Exchange of Picornaviruses in Vietnam between Humans and Animals in a High-Risk Cohort with Close Contact despite High Prevalence and Diversity. Viruses 2021; 13:v13091709. [PMID: 34578290 PMCID: PMC8473303 DOI: 10.3390/v13091709] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/22/2021] [Accepted: 08/23/2021] [Indexed: 02/03/2023] Open
Abstract
Hospital-based and community-based 'high-risk cohort' studies investigating humans at risk of zoonotic infection due to occupational or residential exposure to animals were conducted in Vietnam, with diverse viruses identified from faecal samples collected from humans, domestic and wild animals. In this study, we focus on the positive-sense RNA virus family Picornaviridae, investigating the prevalence, diversity, and potential for cross-species transmission. Through metagenomic sequencing, we found picornavirus contigs in 23% of samples, belonging to 15 picornavirus genera. Prevalence was highest in bats (67%) while diversity was highest in rats (nine genera). In addition, 22% of the contigs were derived from novel viruses: Twelve phylogenetically distinct clusters were observed in rats of which seven belong to novel species or types in the genera Hunnivirus, Parechovirus, Cardiovirus, Mosavirus and Mupivirus; four distinct clusters were found in bats, belonging to one novel parechovirus species and one related to an unclassified picornavirus. There was no evidence for zoonotic transmission in our data. Our study provides an improved knowledge of the diversity and prevalence of picornaviruses, including a variety of novel picornaviruses in rats and bats. We highlight the importance of monitoring the human-animal interface for possible spill-over events.
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Affiliation(s)
- Lu Lu
- Usher Institute, University of Edinburgh, Edinburgh EH9 3FL, UK; (J.A.); (M.W.)
- Correspondence:
| | - Jordan Ashworth
- Usher Institute, University of Edinburgh, Edinburgh EH9 3FL, UK; (J.A.); (M.W.)
| | - Dung Nguyen
- Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; (D.N.); (D.B.S.)
| | - Kejin Li
- Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3FL, UK;
| | - Donald B. Smith
- Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; (D.N.); (D.B.S.)
- Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 3FL, UK;
| | - Mark Woolhouse
- Usher Institute, University of Edinburgh, Edinburgh EH9 3FL, UK; (J.A.); (M.W.)
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25
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Rajput C, Han M, Ishikawa T, Lei J, Goldsmith AM, Jazaeri S, Stroupe CC, Bentley JK, Hershenson MB. Rhinovirus C Infection Induces Type 2 Innate Lymphoid Cell Expansion and Eosinophilic Airway Inflammation. Front Immunol 2021; 12:649520. [PMID: 33968043 PMCID: PMC8100319 DOI: 10.3389/fimmu.2021.649520] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 04/07/2021] [Indexed: 12/21/2022] Open
Abstract
Rhinovirus C (RV-C) infection is associated with severe asthma exacerbations. Since type 2 inflammation is an important disease mechanism in asthma, we hypothesized that RV-C infection, in contrast to RV-A, preferentially stimulates type 2 inflammation, leading to exacerbated eosinophilic inflammation. To test this, we developed a mouse model of RV-C15 airways disease. RV-C15 was generated from the full-length cDNA clone and grown in HeLa-E8 cells expressing human CDHR3. BALB/c mice were inoculated intranasally with 5 x 106 ePFU RV-C15, RV-A1B or sham. Mice inoculated with RV-C15 showed lung viral titers of 1 x 105 TCID50 units 24 h after infection, with levels declining thereafter. IFN-α, β, γ and λ2 mRNAs peaked 24-72 hrs post-infection. Immunofluorescence verified colocalization of RV-C15, CDHR3 and acetyl-α-tubulin in mouse ciliated airway epithelial cells. Compared to RV-A1B, mice infected with RV-C15 demonstrated higher bronchoalveolar eosinophils, mRNA expression of IL-5, IL-13, IL-25, Muc5ac and Gob5/Clca, protein production of IL-5, IL-13, IL-25, IL-33 and TSLP, and expansion of type 2 innate lymphoid cells. Analogous results were found in mice treated with house dust mite before infection, including increased airway responsiveness. In contrast to Rorafl/fl littermates, RV-C-infected Rorafl/flIl7rcre mice deficient in ILC2s failed to show eosinophilic inflammation or mRNA expression of IL-13, Muc5ac and Muc5b. We conclude that, compared to RV-A1B, RV-C15 infection induces ILC2-dependent type 2 airway inflammation, providing insight into the mechanism of RV-C-induced asthma exacerbations.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Marc B. Hershenson
- Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, United States
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26
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Genome sequencing and phylogenetic reconstruction reveal a potential fourth rhinovirus species and its worldwide distribution. Arch Virol 2020; 166:225-229. [PMID: 33084935 DOI: 10.1007/s00705-020-04855-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 09/14/2020] [Indexed: 01/30/2023]
Abstract
Genome sequences of members of a potential fourth rhinovirus (RV) species, provisionally denoted as rhinovirus A clade D, from patients with acute respiratory infection were determined. Bayesian coalescent analysis estimated that clade D emerged around the 1940s and diverged further around 2006-2007 into two distinctive sublineages (RV-A8-like and RV-A45-like) that harbored unique "clade-defining" substitutions. Similarity plots and bootscan mapping revealed a recombination breakpoint located in the 5'-UTR region of members of the RV-A8-like sublineage. Phylogenetic reconstruction revealed the distribution of clade D viruses in the Asia Pacific region and in Europe, underlining its worldwide distribution.
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27
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Luka MM, Kamau E, Adema I, Munywoki PK, Otieno GP, Gicheru E, Gichuki A, Kibinge N, Agoti CN, Nokes DJ. Molecular Epidemiology of Human Rhinovirus From 1-Year Surveillance Within a School Setting in Rural Coastal Kenya. Open Forum Infect Dis 2020; 7:ofaa385. [PMID: 33094115 PMCID: PMC7568438 DOI: 10.1093/ofid/ofaa385] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 08/21/2020] [Indexed: 01/12/2023] Open
Abstract
Background Human rhinovirus (HRV) is the most common cause of the common cold but may also lead to more severe respiratory illness in vulnerable populations. The epidemiology and genetic diversity of HRV within a school setting have not been previously described. The objective of this study was to characterize HRV molecular epidemiology in a primary school in a rural location of Kenya. Methods Between May 2017 and April 2018, over 3 school terms, we collected 1859 nasopharyngeal swabs (NPS) from pupils and teachers with symptoms of acute respiratory infection in a public primary school in Kilifi County, coastal Kenya. The samples were tested for HRV using real-time reverse transcription polymerase chain reaction. HRV-positive samples were sequenced in the VP4/VP2 coding region for species and genotype classification. Results A total of 307 NPS (16.4%) from 164 individuals were HRV positive, and 253 (82.4%) were successfully sequenced. The proportion of HRV in the lower primary classes was higher (19.8%) than upper primary classes (12.2%; P < .001). HRV-A was the most common species (134/253; 53.0%), followed by HRV-C (73/253; 28.9%) and HRV-B (46/253; 18.2%). Phylogenetic analysis identified 47 HRV genotypes. The most common genotypes were A2 and B70. Numerous (up to 22 in 1 school term) genotypes circulated simultaneously, there was no individual re-infection with the same genotype, and no genotype was detected in all 3 school terms. Conclusions HRV was frequently detected among school-going children with mild acute respiratory illness symptoms, particularly in the younger age groups (<5-year-olds). Multiple HRV introductions were observed that were characterized by considerable genotype diversity.
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Affiliation(s)
- Martha M Luka
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, Kilifi, Kenya.,Department of Public Health, Pwani University, Kilifi, Kenya
| | - Everlyn Kamau
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, Kilifi, Kenya
| | - Irene Adema
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, Kilifi, Kenya
| | - Patrick K Munywoki
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, Kilifi, Kenya
| | - Grieven P Otieno
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, Kilifi, Kenya
| | - Elijah Gicheru
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, Kilifi, Kenya
| | - Alex Gichuki
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, Kilifi, Kenya
| | - Nelson Kibinge
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, Kilifi, Kenya
| | - Charles N Agoti
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, Kilifi, Kenya.,Department of Public Health, Pwani University, Kilifi, Kenya
| | - D James Nokes
- Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, Kilifi, Kenya.,School of Life Sciences and Zeeman Institute for Systems Biology and Infectious Disease Epidemiology Research (SBIDER), University of Warwick, Coventry, UK
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28
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Baillie VL, Moore DP, Mathunjwa A, Morailane P, Simões EAF, Madhi SA. A prospective case-control study on the association of Rhinovirus nasopharyngeal viral load and viremia in South African children hospitalized with severe pneumonia. J Clin Virol 2020; 125:104288. [PMID: 32092643 PMCID: PMC7086148 DOI: 10.1016/j.jcv.2020.104288] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 01/30/2020] [Accepted: 02/10/2020] [Indexed: 01/22/2023]
Abstract
Rhinovirus role during severe childhood respiratory disease remains unknown. Rhinovirus prevalence was similar between children with pneumonia and controls. Rhinovirus-viremia was 4-fold more prevalent amongst cases than controls. Viremia could be helpful in attributing causality to rhinovirus during pneumonia episodes. Rhinovirus (RV) role in pathogenesis of severe childhood disease remains controversial. We aimed to explore the association between RV molecular subtyping, nasopharyngeal viral loads and viremia with childhood pneumonia. Nasopharyngeal and blood samples from cases and controls were tested for RV and the 5′ non-coding region sequenced. The cases compared to controls had a similar prevalence of RV detection in the nasopharynx (23 % vs. 22 %, P = 0.66), similar RV species distribution (A, B, C = 44 %, 8%, 44 % vs. 48 %, 7%, 38 %; respectively; P = 0.66) and similar viral load (4.0 and 3.7 log10 copies/mL, P = 0.062). However, RV-viremia was 4.01-fold (aOR 95 % CI: 1.26–12.78) more prevalent among cases (7%) than controls (2%), P = 0.019. Furthermore, among cases and controls RV-C was more commonly associated with viremia (14 % and 4%, P = 0.023), than RV-A (2% and 1%; P = 0.529). Thus RV-viremia could be used as a measure for attributing causality to RV in children hospitalized for pneumonia.
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Affiliation(s)
- Vicky L Baillie
- Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases Chair, South Africa.
| | - David P Moore
- Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases Chair, South Africa
| | - Azwifarwi Mathunjwa
- Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases Chair, South Africa
| | - Palesa Morailane
- Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases Chair, South Africa
| | - Eric A F Simões
- Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases Chair, South Africa; University of Colorado School of Medicine and Colorado School of Public Health, CO, USA
| | - Shabir A Madhi
- Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases Chair, South Africa
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Zhang N, Wang L, Deng X, Liang R, Su M, He C, Hu L, Su Y, Ren J, Yu F, Du L, Jiang S. Recent advances in the detection of respiratory virus infection in humans. J Med Virol 2020; 92:408-417. [PMID: 31944312 PMCID: PMC7166954 DOI: 10.1002/jmv.25674] [Citation(s) in RCA: 308] [Impact Index Per Article: 61.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Accepted: 01/12/2020] [Indexed: 12/20/2022]
Abstract
Respiratory tract viral infection caused by viruses or bacteria is one of the most common diseases in human worldwide, while those caused by emerging viruses, such as the novel coronavirus, 2019‐nCoV that caused the pneumonia outbreak in Wuhan, China most recently, have posed great threats to global public health. Identification of the causative viral pathogens of respiratory tract viral infections is important to select an appropriate treatment, save people's lives, stop the epidemics, and avoid unnecessary use of antibiotics. Conventional diagnostic tests, such as the assays for rapid detection of antiviral antibodies or viral antigens, are widely used in many clinical laboratories. With the development of modern technologies, new diagnostic strategies, including multiplex nucleic acid amplification and microarray‐based assays, are emerging. This review summarizes currently available and novel emerging diagnostic methods for the detection of common respiratory viruses, such as influenza virus, human respiratory syncytial virus, coronavirus, human adenovirus, and human rhinovirus. Multiplex assays for simultaneous detection of multiple respiratory viruses are also described. It is anticipated that such data will assist researchers and clinicians to develop appropriate diagnostic strategies for timely and effective detection of respiratory virus infections.
Respiratory tract viral infection including 2019‐nCoV poses great threats worldwide. Currently available and novel emerging diagnostic methods are summarized for several common respiratory viruses, including influenza virus, human respiratory syncytial virus, coronavirus, human adenovirus and human rhinovirus. Multiplex assays for simultaneous detection of multiple respiratory viruses are also described. This review is aimed to assist researchers and clinicians to develop timely and effective diagnostic strategies to detect respiratory virus infections.
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Affiliation(s)
- Naru Zhang
- Department of Clinical Medicine, School of Medicine, Zhejiang University City College, Hangzhou, China
| | - Lili Wang
- State Key Laboratory of North China Crop Improvement and Regulation, Research Center of Chinese Jujube, Hebei Agricultural University, Baoding, China
| | - Xiaoqian Deng
- State Key Laboratory of North China Crop Improvement and Regulation, College of Life and Science, Hebei Agricultural University, Baoding, China
| | - Ruiying Liang
- State Key Laboratory of North China Crop Improvement and Regulation, College of Life and Science, Hebei Agricultural University, Baoding, China
| | - Meng Su
- State Key Laboratory of North China Crop Improvement and Regulation, College of Life and Science, Hebei Agricultural University, Baoding, China
| | - Chen He
- State Key Laboratory of North China Crop Improvement and Regulation, College of Life and Science, Hebei Agricultural University, Baoding, China
| | - Lanfang Hu
- State Key Laboratory of North China Crop Improvement and Regulation, College of Life and Science, Hebei Agricultural University, Baoding, China
| | - Yudan Su
- State Key Laboratory of North China Crop Improvement and Regulation, College of Life and Science, Hebei Agricultural University, Baoding, China
| | - Jing Ren
- State Key Laboratory of North China Crop Improvement and Regulation, College of Life and Science, Hebei Agricultural University, Baoding, China
| | - Fei Yu
- State Key Laboratory of North China Crop Improvement and Regulation, College of Life and Science, Hebei Agricultural University, Baoding, China
| | - Lanying Du
- Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York
| | - Shibo Jiang
- Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York.,Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China
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Han AX, Parker E, Scholer F, Maurer-Stroh S, Russell CA. Phylogenetic Clustering by Linear Integer Programming (PhyCLIP). Mol Biol Evol 2020; 36:1580-1595. [PMID: 30854550 PMCID: PMC6573476 DOI: 10.1093/molbev/msz053] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Subspecies nomenclature systems of pathogens are increasingly based on sequence data. The use of phylogenetics to identify and differentiate between clusters of genetically similar pathogens is particularly prevalent in virology from the nomenclature of human papillomaviruses to highly pathogenic avian influenza (HPAI) H5Nx viruses. These nomenclature systems rely on absolute genetic distance thresholds to define the maximum genetic divergence tolerated between viruses designated as closely related. However, the phylogenetic clustering methods used in these nomenclature systems are limited by the arbitrariness of setting intra and intercluster diversity thresholds. The lack of a consensus ground truth to define well-delineated, meaningful phylogenetic subpopulations amplifies the difficulties in identifying an informative distance threshold. Consequently, phylogenetic clustering often becomes an exploratory, ad hoc exercise. Phylogenetic Clustering by Linear Integer Programming (PhyCLIP) was developed to provide a statistically principled phylogenetic clustering framework that negates the need for an arbitrarily defined distance threshold. Using the pairwise patristic distance distributions of an input phylogeny, PhyCLIP parameterizes the intra and intercluster divergence limits as statistical bounds in an integer linear programming model which is subsequently optimized to cluster as many sequences as possible. When applied to the hemagglutinin phylogeny of HPAI H5Nx viruses, PhyCLIP was not only able to recapitulate the current WHO/OIE/FAO H5 nomenclature system but also further delineated informative higher resolution clusters that capture geographically distinct subpopulations of viruses. PhyCLIP is pathogen-agnostic and can be generalized to a wide variety of research questions concerning the identification of biologically informative clusters in pathogen phylogenies. PhyCLIP is freely available at http://github.com/alvinxhan/PhyCLIP, last accessed March 15, 2019.
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Affiliation(s)
- Alvin X Han
- Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore.,NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore (NUS), Singapore.,Laboratory of Applied Evolutionary Biology, Department of Medical Microbiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - Edyth Parker
- Laboratory of Applied Evolutionary Biology, Department of Medical Microbiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.,Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Frits Scholer
- Department of Medical Microbiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - Sebastian Maurer-Stroh
- Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore.,NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore (NUS), Singapore.,Department of Biological Sciences, National University of Singapore, Singapore
| | - Colin A Russell
- Laboratory of Applied Evolutionary Biology, Department of Medical Microbiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
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31
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Arden KE, Greer RM, Wang CYT, Mackay IM. Genotypic diversity, circulation patterns and co-detections among rhinoviruses in Queensland, 2001. Access Microbiol 2019; 2:acmi000075. [PMID: 33062934 PMCID: PMC7525053 DOI: 10.1099/acmi.0.000075] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Accepted: 10/07/2019] [Indexed: 12/13/2022] Open
Abstract
Purpose Rhinoviruses (RVs) occur more frequently than other viruses and more often in people displaying symptoms than in those without. We sought to estimate the spectrum of RV diversity, RV species seasonality and to analyse RV involvement in respiratory virus co-detections. Methodology A convenience collection of 1179 airway sample extracts from patients with suspected respiratory infections, collected during 2001, was subjected to comprehensive molecular testing. Results RVs were the most common virus detected. We were able to genotype ~90 % of RV detections, identifying 70 distinct RVs, spanning all three species. RV-Bs were under-represented. We found RV species co-circulated at times, although one species usually dominated. Each species displayed a bimodal distribution. Conclusion Notably, RVs and influenza A viruses (IFAV) seldom co-occurred, supporting their roles as primary pathogens of the airway among acutely ill infants. Whether RV circulation has a moderating or controlling effect on the IFAV season or is controlled by it cannot be determined from these data. Despite the frequent perception that RVs commonly co-occur with another virus, our findings indicated this was not always the case. Nearly 80 % of RV detections occurred alone. Understanding more about population-level interference between viruses may allow us to harness aspects of it to generate a non-specific antiviral intervention that mimics a putative protective effect. For routine respiratory virus screening to best serve the patient, RV testing should be a principal component of any acute respiratory illness testing algorithm throughout the year.
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Affiliation(s)
- Katherine E Arden
- Child Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia
| | - Ristan M Greer
- Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Claire Y T Wang
- Child Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia.,Centre for Children's Health Research, Children's Health Queensland South Brisbane, Queensland, 4101, Australia
| | - Ian M Mackay
- Child Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia
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Molecular Subtyping of Human Rhinovirus in Children from Three Sub-Saharan African Countries. J Clin Microbiol 2019; 57:JCM.00723-19. [PMID: 31270180 PMCID: PMC6711929 DOI: 10.1128/jcm.00723-19] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 06/24/2019] [Indexed: 11/20/2022] Open
Abstract
The pathogenesis of human rhinovirus (HRV) during severe respiratory disease remains undefined; thus, we aimed to explore the relationship between the HRV molecular subtyping results obtained during severe and asymptomatic childhood infections. Nasopharyngeal/oropharyngeal swabs from children (1 to 59 months of age) hospitalized with pneumonia and from age-frequency-matched controls were collected between August 2011 and August 2013. The pathogenesis of human rhinovirus (HRV) during severe respiratory disease remains undefined; thus, we aimed to explore the relationship between the HRV molecular subtyping results obtained during severe and asymptomatic childhood infections. Nasopharyngeal/oropharyngeal swabs from children (1 to 59 months of age) hospitalized with pneumonia and from age-frequency-matched controls were collected between August 2011 and August 2013. Swabs were tested for respiratory pathogens, including HRV, using quantitative real-time PCR assays. HRV-positive samples were sequenced for phylogenetic analysis by targeting the 5′ noncoding region (5′NCR). Our data showed that there were no differences in the prevalence of HRV detection among cases and controls (21% versus 20%, P = 0.693); however, among children 13 to 59 months old, HRV detection was more often case associated (21% versus 16%; P = 0.009), with the results mainly driven by HRV-C (12% versus 7%; P = 0.001). Overall, there were no differences in the results of molecular subtyping of the HRV species prevalence among cases (for HRV-A, 48%; for HRV-B, 7%; for HRV-C, 45%) and controls (for HRV-A, 45%; for HRV-B, 10%; for HRV-C, 45% [P = 0.496]). Those with pneumonia and HRV-C were older (12.1 versus 9.4 months, P = 0.033) and more likely to present with wheeze (35% versus 25%, P = 0.031) than those with HRV-A cases. Thus, the rate of HRV detection was high, with similar degrees of genetic diversity among cases and controls, confounding the interpretation of the presence of HRV in nasopharyngeal samples for attribution of a causal role in the pathogenesis of severe pneumonia in infants. However, among children 13 to 59 months of age, HRV detection, in particular, HRV-C detection, was associated with case status, especially among children with wheezing disease.
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Tirosh O, Conlan S, Deming C, Lee-Lin SQ, Huang X, Su HC, Freeman AF, Segre JA, Kong HH. Expanded skin virome in DOCK8-deficient patients. Nat Med 2018; 24:1815-1821. [PMID: 30397357 PMCID: PMC6286253 DOI: 10.1038/s41591-018-0211-7] [Citation(s) in RCA: 90] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Accepted: 09/05/2018] [Indexed: 12/25/2022]
Abstract
Human microbiome studies have revealed the intricate interplay of host immunity and bacterial communities to achieve homeostatic balance. Healthy skin microbial communities are dominated by bacteria with low viral representation1-3, mainly bacteriophage. Specific eukaryotic viruses have been implicated in both common and rare skin diseases, but cataloging skin viral communities has been limited. Alterations in host immunity provide an opportunity to expand our understanding of microbial-host interactions. Primary immunodeficient patients manifest with various viral, bacterial, fungal, and parasitic infections, including skin infections4. Dedicator of cytokinesis 8 (DOCK8) deficiency is a rare primary human immunodeficiency characterized by recurrent cutaneous and systemic infections, as well as atopy and cancer susceptibility5. DOCK8, encoding a guanine nucleotide exchange factor highly expressed in lymphocytes, regulates actin cytoskeleton, which is critical for migration through collagen-dense tissues such as skin6. Analyzing deep metagenomic sequencing data from DOCK8-deficient skin samples demonstrated a notable increase in eukaryotic viral representation and diversity compared with healthy volunteers. De novo assembly approaches identified hundreds of novel human papillomavirus genomes, illuminating microbial dark matter. Expansion of the skin virome in DOCK8-deficient patients underscores the importance of immune surveillance in controlling eukaryotic viral colonization and infection.
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Affiliation(s)
- Osnat Tirosh
- Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA
| | - Sean Conlan
- Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA
| | - Clay Deming
- Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA
| | - Shih-Queen Lee-Lin
- Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA
| | - Xin Huang
- Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA
| | - Helen C Su
- Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
| | - Alexandra F Freeman
- Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA
| | - Julia A Segre
- Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA.
| | - Heidi H Kong
- Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
- Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD, USA.
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Andrés C, Peremiquel-Trillas P, Gimferrer L, Isern A, Piñana M, Rodrigo-Pendás JÁ, Codina MG, Martín MDC, Fuentes F, Rubio S, Campins-Martí M, Pumarola T, Antón A. Genetic diversity of rhinoviruses detected at a tertiary hospital in Catalonia (Spain) during the 2014-2017 seasons. Future Microbiol 2018; 13:1565-1573. [PMID: 30417657 DOI: 10.2217/fmb-2018-0151] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
AIM To describe the genetic diversity of rhinovirus (RV) from patients attended at a tertiary hospital in Barcelona (Spain) from October 2014 to May 2017. METHODS RV detection was performed by real-time multiplex RT-PCR. A specific real-time quantitive retrotranscription PCR (qRT-PCR) was carried out to select those samples (Ct < 35) for molecular characterization based on partial VP4/2 protein. RESULTS Phylogenetic characterization revealed proportions of 63% RV-A, 6% RV-B and 31% RV-C (119 different types). RV-A circulated throughout all the study period, with a minor circulation during winter, just when RV-C prevailed. Differences between age medians by RV-specie were reported. CONCLUSION The large genetic diversity of RV detected in our area is described here. The variable cocirculation of multiple RV types is also reported, showing differences by age.
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Affiliation(s)
- Cristina Andrés
- Respiratory Viruses Unit, Virology Section, Microbiology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Paula Peremiquel-Trillas
- Preventive Medicine & Epidemiology Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Vall Hebron Research Institute, Barcelona, Spain
| | - Laura Gimferrer
- Respiratory Viruses Unit, Virology Section, Microbiology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Anna Isern
- Respiratory Viruses Unit, Virology Section, Microbiology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Maria Piñana
- Respiratory Viruses Unit, Virology Section, Microbiology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - José Ángel Rodrigo-Pendás
- Preventive Medicine & Epidemiology Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Vall Hebron Research Institute, Barcelona, Spain
| | - Maria Gema Codina
- Respiratory Viruses Unit, Virology Section, Microbiology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - María Del Carmen Martín
- Respiratory Viruses Unit, Virology Section, Microbiology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Francisco Fuentes
- Respiratory Viruses Unit, Virology Section, Microbiology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Susana Rubio
- Respiratory Viruses Unit, Virology Section, Microbiology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Magda Campins-Martí
- Preventive Medicine & Epidemiology Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Vall Hebron Research Institute, Barcelona, Spain
| | - Tomàs Pumarola
- Respiratory Viruses Unit, Virology Section, Microbiology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Andrés Antón
- Respiratory Viruses Unit, Virology Section, Microbiology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
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Nikonov OS, Chernykh ES, Garber MB, Nikonova EY. Enteroviruses: Classification, Diseases They Cause, and Approaches to Development of Antiviral Drugs. BIOCHEMISTRY (MOSCOW) 2018. [PMID: 29523062 PMCID: PMC7087576 DOI: 10.1134/s0006297917130041] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The genus Enterovirus combines a portion of small (+)ssRNA-containing viruses and is divided into 10 species of true enteroviruses and three species of rhinoviruses. These viruses are causative agents of the widest spectrum of severe and deadly epidemic diseases of higher vertebrates, including humans. Their ubiquitous distribution and high pathogenici- ty motivate active search to counteract enterovirus infections. There are no sufficiently effective drugs targeted against enteroviral diseases, thus treatment is reduced to supportive and symptomatic measures. This makes it extremely urgent to develop drugs that directly affect enteroviruses and hinder their development and spread in infected organisms. In this review, we cover the classification of enteroviruses, mention the most common enterovirus infections and their clinical man- ifestations, and consider the current state of development of anti-enteroviral drugs. One of the most promising targets for such antiviral drugs is the viral Internal Ribosome Entry Site (IRES). The classification of these elements of the viral mRNA translation system is also examined.
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Affiliation(s)
- O S Nikonov
- Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia.
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36
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Stobart CC, Nosek JM, Moore ML. Rhinovirus Biology, Antigenic Diversity, and Advancements in the Design of a Human Rhinovirus Vaccine. Front Microbiol 2017; 8:2412. [PMID: 29259600 PMCID: PMC5723287 DOI: 10.3389/fmicb.2017.02412] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Accepted: 11/21/2017] [Indexed: 01/06/2023] Open
Abstract
Human rhinovirus (HRV) remains a leading cause of several human diseases including the common cold. Despite considerable research over the last 60 years, development of an effective vaccine to HRV has been viewed by many as unfeasible due, in part, to the antigenic diversity of circulating HRVs in nature. Over 150 antigenically distinct types of HRV are currently known which span three species: HRV A, HRV B, and HRV C. Early attempts to develop a rhinovirus vaccine have shown that inactivated HRV is capable of serving as a strong immunogen and inducing neutralizing antibodies. Yet, limitations to virus preparation and recovery, continued identification of antigenic variants of HRV, and logistical challenges pertaining to preparing a polyvalent preparation of the magnitude required for true efficacy against circulating rhinoviruses continue to prove a daunting challenge. In this review, we describe HRV biology, antigenic diversity, and past and present advances in HRV vaccine design.
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Affiliation(s)
- Christopher C Stobart
- Department of Biological Sciences, Butler University, Indianapolis, IN, United States
| | - Jenna M Nosek
- Department of Biological Sciences, Butler University, Indianapolis, IN, United States
| | - Martin L Moore
- Department of Pediatrics, Emory University, Atlanta, GA, United States.,Children's Healthcare of Atlanta, Atlanta, GA, United States
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Complete Genome Sequence of a Divergent Human Rhinovirus C Isolate from an Infant with Severe Community-Acquired Pneumonia in Colorado, USA. GENOME ANNOUNCEMENTS 2017; 5:5/48/e01245-17. [PMID: 29192071 PMCID: PMC5722057 DOI: 10.1128/genomea.01245-17] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Here, we report the genome sequence of a divergent human rhinovirus C isolate identified from an infant with a severe community-acquired respiratory infection. RNA sequencing performed on an Illumina platform identified reads aligning to human rhinovirus species, which were de novo assembled to produce a coding-complete genome sequence.
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38
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Zheng SY, Wang LL, Ren L, Luo J, Liao W, Liu EM. Epidemiological analysis and follow-up of human rhinovirus infection in children with asthma exacerbation. J Med Virol 2017; 90:219-228. [PMID: 28500687 PMCID: PMC7167043 DOI: 10.1002/jmv.24850] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2016] [Accepted: 04/19/2017] [Indexed: 12/20/2022]
Abstract
To determine the prevalence of human rhinovirus (HRV) infection in children with acute asthma exacerbations, investigation of HRV viral load and severity of asthma exacerbations is also required. Nasopharyngeal aspirates and swabs were collected and assessed for respiratory viruses. HRV-positive samples were sequenced to identify types and determine viral load. Outpatients with asthma exacerbations underwent follow-up evaluations, their swabs were collected and clinical outcomes were recorded at their next clinic visit 4 weeks later. One hundred forty-three inpatients and 131 outpatients, including 88 patients with asthma exacerbations and 43 controls with stable asthma were recruited. HRV-A was mainly detected in September and February (45.5% and 33.3%, respectively), while HRV-C was mainly detected in November and April (70.0% and 55.6%, respectively). HRV-C was the primary type and was primarily found in inpatients with severe asthma exacerbations. HRV-A viral load in the group of inpatients with severe exacerbations was higher than in the mild and moderate groups (P < 0.001 and P = 0.022). The HRV-A viral load of both inpatients and outpatients was higher than that of HRV-C (P < 0.001 and P = 0.036). The main genotypes were HRV-C53 and HRV-A20 among inpatients, and this genotype caused more severe clinical manifestations. HRV persisted for no more than 4 weeks, and their symptoms or signs of disease were well-controlled well. HRV-C was most frequently detected in asthma exacerbations. HRV-A with high viral load led to severe asthma exacerbations.
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Affiliation(s)
- Shou-Yan Zheng
- Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China
| | - Li-Li Wang
- Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China
| | - Luo Ren
- Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China
| | - Jian Luo
- Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Wei Liao
- Department of Pediatrics, Southwest Hospital of The Third Military Medical University, Chongqing, China
| | - En-Mei Liu
- Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing, China
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39
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Patel MC, Pletneva LM, Boukhvalova MS, Vogel SN, Kajon AE, Blanco JCG. Immunization with Live Human Rhinovirus (HRV) 16 Induces Protection in Cotton Rats against HRV14 Infection. Front Microbiol 2017; 8:1646. [PMID: 28912760 PMCID: PMC5583225 DOI: 10.3389/fmicb.2017.01646] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Accepted: 08/15/2017] [Indexed: 11/13/2022] Open
Abstract
Human rhinoviruses (HRVs) are the main cause of cold-like illnesses, and currently no vaccine or antiviral therapies against HRVs are available to prevent or mitigate HRV infection. There are more than 150 antigenically heterogeneous HRV serotypes, with ∼90 HRVs belonging to major group species A and B. Development of small animal models that are susceptible to infection with major group HRVs would be beneficial for vaccine research. Previously, we showed that the cotton rat (Sigmodon hispidus) is semi-permissive to HRV16 (major group, species HRV-A virus) infection, replicating in the upper and lower respiratory tracts with measurable pathology, mucus production, and expression of inflammatory mediators. Herein, we report that intranasal infection of cotton rats with HRV14 (major group, species HRV-B virus) results in isolation of infectious virus from the nose and lung. Similar to HRV16, intramuscular immunization with live HRV14 induces homologous protection that correlated with high levels of serum neutralizing antibodies. Vaccination and challenge experiments with HRV14 and HRV16 to evaluate the development of cross-protective immunity demonstrate that intramuscular immunization with live HRV16 significantly protects animals against HRV14 challenge. Determination of the immunological mechanisms involved in heterologous protection and further characterization of infection with other major HRV serotypes in the cotton rat could enhance the robustness of the model to define heterotypic relationships between this diverse group of viruses and thereby increase its potential for development of a multi-serotype HRV vaccine.
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Affiliation(s)
- Mira C Patel
- Sigmovir Biosystems, Inc., RockvilleMD, United States
| | | | | | - Stefanie N Vogel
- University of Maryland School of Medicine, BaltimoreMD, United States
| | - Adriana E Kajon
- Infectious Disease Program, Lovelace Respiratory Research Institute, AlbuquerqueNM, United States
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40
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Sopel N, Pflaum A, Kölle J, Finotto S. The Unresolved Role of Interferon-λ in Asthma Bronchiale. Front Immunol 2017; 8:989. [PMID: 28861088 PMCID: PMC5559474 DOI: 10.3389/fimmu.2017.00989] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Accepted: 08/02/2017] [Indexed: 12/20/2022] Open
Abstract
Asthma bronchiale is a disease of the airways with increasing incidence, that often begins during infancy. So far, therapeutic options are mainly symptomatic and thus there is an increasing need for better treatment and/or prevention strategies. Human rhinoviruses (HRVs) are a major cause of asthma exacerbations and might cause acute wheezing associated with local production of pro-inflammatory mediators resulting in neutrophilic inflammatory response. Viral infections induce a characteristic activation of immune response, e.g., TLR3, 4, 7, 8, 9 in the endosome and their downstream targets, especially MyD88. Moreover, other cytoplasmic pattern recognition molecules (PRMs) like RIG1 and MDA5 play important roles in the activation of interferons (IFNs) of all types. Depending on the stimulation of the different PRMs, the levels of the IFNs induced might differ. Recent studies focused on Type I IFNs in samples from control and asthma patients. However, the administration of type I IFN-α was accompanied by side-effects, thus this possible therapy was abandoned. Type III IFN-λ acts more specifically, as fewer cells express the IFN-λ receptor chain 1. In addition, it has been shown that asthmatic mice treated with recombinant or adenoviral expressed IFN-λ2 (IL–28A) showed an amelioration of symptoms, indicating that treatment with IFN-λ might be beneficial for asthmatic patients.
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Affiliation(s)
- Nina Sopel
- Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
| | - Andreas Pflaum
- Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
| | - Julia Kölle
- Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
| | - Susetta Finotto
- Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
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Stelzer-Braid S, Liu N, Doumit M, D'Cunha R, Belessis Y, Jaffe A, Rawlinson WD. Association of rhinovirus with exacerbations in young children affected by cystic fibrosis: Preliminary data. J Med Virol 2017; 89:1494-1497. [PMID: 28213960 DOI: 10.1002/jmv.24794] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Accepted: 02/09/2017] [Indexed: 11/10/2022]
Abstract
Rhinovirus (RV) is a common respiratory viral infection linked to worsening of chronic respiratory diseases including cystic fibrosis (CF) and asthma. RV was tested by RT-PCR in samples (n = 465) collected from the upper (nasal swab, oropharyngeal suction, and sputum) and lower (bronchoalveolar washings) respiratory tract of 110 children with CF. Air samples (n = 52) collected from the operating theatres and outpatient clinics were tested for RV. RV was found in 43% of children <5 years suffering an exacerbation, and 12% of older children (5-17 years). RV particles were detected in the air of clinic rooms. Detection of RV is important in better understanding viral infections in patients with CF.
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Affiliation(s)
- Sacha Stelzer-Braid
- Virology Research Laboratory, Prince of Wales Hospital, New South Wales, Australia.,Faculty of Medicine, School of Medical Sciences, University of New South Wales, Sydney, Australia
| | - Nancy Liu
- Virology Research Laboratory, Prince of Wales Hospital, New South Wales, Australia.,Faculty of Medicine, School of Medical Sciences, University of New South Wales, Sydney, Australia
| | - Michael Doumit
- Sydney Children's Hospital, New South Wales, Australia.,Faculty of Medicine, School of Women's and Children's Health, University of New South Wales, Sydney, Australia
| | - Russell D'Cunha
- Virology Research Laboratory, Prince of Wales Hospital, New South Wales, Australia.,Faculty of Medicine, School of Medical Sciences, University of New South Wales, Sydney, Australia
| | - Yvonne Belessis
- Sydney Children's Hospital, New South Wales, Australia.,Faculty of Medicine, School of Women's and Children's Health, University of New South Wales, Sydney, Australia
| | - Adam Jaffe
- Sydney Children's Hospital, New South Wales, Australia.,Faculty of Medicine, School of Women's and Children's Health, University of New South Wales, Sydney, Australia
| | - William D Rawlinson
- Virology Research Laboratory, Prince of Wales Hospital, New South Wales, Australia.,Faculty of Medicine, School of Medical Sciences, University of New South Wales, Sydney, Australia
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Bochkov YA, Watters K, Basnet S, Sijapati S, Hill M, Palmenberg AC, Gern JE. Mutations in VP1 and 3A proteins improve binding and replication of rhinovirus C15 in HeLa-E8 cells. Virology 2016; 499:350-360. [PMID: 27743961 PMCID: PMC5110265 DOI: 10.1016/j.virol.2016.09.025] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Revised: 09/24/2016] [Accepted: 09/26/2016] [Indexed: 11/21/2022]
Abstract
Viruses in the rhinovirus C species (RV-C) can cause severe respiratory illnesses in children including pneumonia and asthma exacerbations. A transduced cell line (HeLa-E8) stably expressing the CDHR3-Y529 receptor variant, supports propagation of RV-C after infection. C15 clinical or recombinant isolates replicate in HeLa-E8, however progeny yields are lower than those of related strains of RV-A and RV-B. Serial passaging of C15 in HeLa-E8 resulted in stronger cytopathic effects and increased (≥10-fold) virus binding to cells and progeny yields. The adaptation was acquired by two mutations which increased binding (VP1 T125K) and replication (3A E41K), respectively. A similar 3A mutation engineered into C2 and C41 cDNAs also improved viral replication (2-8 fold) in HeLa but the heparan sulfate mediated cell-binding enhancement by the VP1 change was C15-specific. The findings now enable large-scale cost-effective C15 production by infection and the testing of RV-C infectivity by plaque assay.
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Affiliation(s)
- Yury A Bochkov
- Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA.
| | - Kelly Watters
- Institute for Molecular Virology, University of Wisconsin-Madison, Madison, WI, USA
| | - Sarmila Basnet
- Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA
| | - Shakher Sijapati
- Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA
| | - Marchel Hill
- Institute for Molecular Virology, University of Wisconsin-Madison, Madison, WI, USA
| | - Ann C Palmenberg
- Institute for Molecular Virology, University of Wisconsin-Madison, Madison, WI, USA
| | - James E Gern
- Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA; Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA
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Bochkov YA, Gern JE. Rhinoviruses and Their Receptors: Implications for Allergic Disease. Curr Allergy Asthma Rep 2016; 16:30. [PMID: 26960297 DOI: 10.1007/s11882-016-0608-7] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Human rhinoviruses (RVs) are picornaviruses that can cause a variety of illnesses including the common cold, lower respiratory tract illnesses such as bronchitis and pneumonia, and exacerbations of asthma. RVs are classified into three species, RV-A, B, and C, which include over 160 types. They utilize three major types of cellular membrane glycoproteins to gain entry into the host cell: intercellular adhesion molecule 1 (ICAM-1) (the majority of RV-A and all RV-B), low-density lipoprotein receptor (LDLR) family members (12 RV-A types), and cadherin-related family member 3 (CDHR3) (RV-C). CDHR3 is a member of cadherin superfamily of transmembrane proteins with yet unknown biological function, and there is relatively little information available about the mechanisms of RV-C interaction with CDHR3. A coding single nucleotide polymorphism (rs6967330) in CDHR3 could promote RV-C infections and illnesses in infancy, which could in turn adversely affect the developing lung to increase the risk of asthma. Further studies are needed to determine how RV infections contribute to pathogenesis of asthma and to develop the optimal treatment approach to control asthma exacerbations.
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Affiliation(s)
- Yury A Bochkov
- Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI, 53792, USA.
| | - James E Gern
- Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI, 53792, USA.,Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI, 53792, USA
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Turunen R, Jartti T, Bochkov YA, Gern JE, Vuorinen T. Rhinovirus species and clinical characteristics in the first wheezing episode in children. J Med Virol 2016; 88:2059-2068. [PMID: 27232888 PMCID: PMC5140033 DOI: 10.1002/jmv.24587] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/25/2016] [Indexed: 12/11/2022]
Abstract
The clinical data on the first wheezing episodes induced by different rhinovirus (RV) species are still limited. We aimed to investigate the prevalence of RV genotypes, sensitization status, and clinical characteristics of patients having a respiratory infection caused by either different RV species or other respiratory viruses. The study enrolled 111 patients (aged 3–23 months, 79% hospitalized, 76% with RV infection) with the first wheezing episode. RV‐specific sequences were identified by partial sequencing of VP4/VP2 and 5′ non‐coding regions with 80% success rate. The investigated clinical and laboratory variables included atopic characteristics and illness severity, parental atopic illnesses, and parental smoking. Of the study children, 56% percent had >1 atopic characteristic (atopy, eczema and/or blood eosinophil count >0.4 × 109/L) and 23% were sensitised to allergens. RV‐C was detected in 58% of RV positive samples, followed by RV‐A (20%) and RV‐B (1.2%). Children with RV‐A and RV‐C induced wheezing were older (P = 0.014) and had more atopic characteristics (P = 0.001) than those with non‐RV. RV‐A and RV‐C illnesses had shorter duration of preadmission symptoms and required more bronchodilator use at the ward than non‐RV illnesses (both P < 0.05, respectively). RV‐C is the most common cause of severe early wheezing. Atopic and illness severity features are associated with children having RV‐A or RV‐C induced first wheezing episode rather than with children having a non‐RV induced wheezing. J. Med. Virol. 88:2059–2068, 2016. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Riitta Turunen
- Department of Pediatrics, Turku University Hospital, Turku, Finland. .,Department of Virology, University of Turku, Finland.
| | - Tuomas Jartti
- Department of Pediatrics, Turku University Hospital, Turku, Finland
| | - Yury A Bochkov
- Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - James E Gern
- Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.,Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Tytti Vuorinen
- Department of Virology, University of Turku, Finland.,Division of Microbiology and Genetics, Department of Clinical Virology, Turku University Hospital, Turku, Finland
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Khaw YS, Chan YF, Jafar FL, Othman N, Chee HY. Comparative Genetic Analyses of Human Rhinovirus C (HRV-C) Complete Genome from Malaysia. Front Microbiol 2016; 7:543. [PMID: 27199901 PMCID: PMC4851184 DOI: 10.3389/fmicb.2016.00543] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2016] [Accepted: 04/04/2016] [Indexed: 11/17/2022] Open
Abstract
Human rhinovirus-C (HRV-C) has been implicated in more severe illnesses than HRV-A and HRV-B, however, the limited number of HRV-C complete genomes (complete 5′ and 3′ non-coding region and open reading frame sequences) has hindered the in-depth genetic study of this virus. This study aimed to sequence seven complete HRV-C genomes from Malaysia and compare their genetic characteristics with the 18 published HRV-Cs. Seven Malaysian HRV-C complete genomes were obtained with newly redesigned primers. The seven genomes were classified as HRV-C6, C12, C22, C23, C26, C42, and pat16 based on the VP4/VP2 and VP1 pairwise distance threshold classification. Five of the seven Malaysian isolates, namely, 3430-MY-10/C22, 8713-MY-10/C23, 8097-MY-11/C26, 1570-MY-10/C42, and 7383-MY-10/pat16 are the first newly sequenced complete HRV-C genomes. All seven Malaysian isolates genomes displayed nucleotide similarity of 63–81% among themselves and 63–96% with other HRV-Cs. Malaysian HRV-Cs had similar putative immunogenic sites, putative receptor utilization and potential antiviral sites as other HRV-Cs. The genomic features of Malaysian isolates were similar to those of other HRV-Cs. Negative selections were frequently detected in HRV-Cs complete coding sequences indicating that these sequences were under functional constraint. The present study showed that HRV-Cs from Malaysia have diverse genetic sequences but share conserved genomic features with other HRV-Cs. This genetic information could provide further aid in the understanding of HRV-C infection.
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Affiliation(s)
- Yam Sim Khaw
- Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Malaysia
| | - Yoke Fun Chan
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya Kuala Lumpur, Malaysia
| | - Faizatul Lela Jafar
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya Kuala Lumpur, Malaysia
| | - Norlijah Othman
- Department of Paediatrics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Malaysia
| | - Hui Yee Chee
- Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Serdang, Malaysia
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Da Costa L, Roche M, Scheers E, Coluccia A, Neyts J, Terme T, Leyssen P, Silvestri R, Vanelle P. VP1 crystal structure-guided exploration and optimization of 4,5-dimethoxybenzene-based inhibitors of rhinovirus 14 infection. Eur J Med Chem 2016; 115:453-62. [PMID: 27049678 DOI: 10.1016/j.ejmech.2016.03.049] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2016] [Revised: 03/17/2016] [Accepted: 03/18/2016] [Indexed: 01/26/2023]
Abstract
Human rhinoviruses (HRV) are the predominant cause of common colds and flu-like illnesses, but are also responsible for virus-induced exacerbations of asthma and chronic obstructive pulmonary disease. However, to date, no drug has been approved yet for clinical use. In this study, we present the results of the structure-based lead optimization of a class of new small-molecule inhibitors that we previously reported to bind into the pocket beneath the canyon of the VP1 protein. A small series of analogues that we designed based on the available structure and interaction data were synthesized and evaluated for their potency to inhibit the replication of HRV serotype 14. 2-(4,5-Dimethoxy-2-nitrophenyl)-1-(4-(pyridin-4-yl)phenyl)ethanol (3v) was found to be a potent inhibitor exhibiting micromolar activity (EC50 = 3.4 ± 1.0 μM) with a toxicity for HeLa cells that was significantly lower than that of our previous hit (LPCRW_0005, CC50 = 104.0 ± 22.2 μM; 3v, CC50 > 263 μM).
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Affiliation(s)
- Laurène Da Costa
- Aix-Marseille Université, Institut de Chimie Radicalaire, UMR 7273 CNRS, 27 Boulevard Jean Moulin, Marseille, France
| | - Manon Roche
- Aix-Marseille Université, Institut de Chimie Radicalaire, UMR 7273 CNRS, 27 Boulevard Jean Moulin, Marseille, France
| | - Els Scheers
- KU Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium
| | - Antonio Coluccia
- Institut Pasteur Italy, Department of Drug Chemistry and Technologies, Sapienza University, I-00185 Rome, Italy
| | - Johan Neyts
- KU Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium.
| | - Thierry Terme
- Aix-Marseille Université, Institut de Chimie Radicalaire, UMR 7273 CNRS, 27 Boulevard Jean Moulin, Marseille, France
| | - Pieter Leyssen
- KU Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium
| | - Romano Silvestri
- Institut Pasteur Italy, Department of Drug Chemistry and Technologies, Sapienza University, I-00185 Rome, Italy.
| | - Patrice Vanelle
- Aix-Marseille Université, Institut de Chimie Radicalaire, UMR 7273 CNRS, 27 Boulevard Jean Moulin, Marseille, France.
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Kolekar PS, Waman VP, Kale MM, Kulkarni-Kale U. RV-Typer: A Web Server for Typing of Rhinoviruses Using Alignment-Free Approach. PLoS One 2016; 11:e0149350. [PMID: 26870949 PMCID: PMC4752186 DOI: 10.1371/journal.pone.0149350] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Accepted: 01/29/2016] [Indexed: 11/24/2022] Open
Abstract
Rhinoviruses (RV) are increasingly being reported to cause mild to severe infections of respiratory tract in humans. RV are antigenically the most diverse species of the genus Enterovirus and family Picornaviridae. There are three species of RV (RV-A, -B and -C), with 80, 32 and 55 serotypes/types, respectively. Antigenic variation is the main limiting factor for development of a cross-protective vaccine against RV.Serotyping of Rhinoviruses is carried out using cross-neutralization assays in cell culture. However, these assays become laborious and time-consuming for the large number of strains. Alternatively, serotyping of RV is carried out by alignment-based phylogeny of both protein and nucleotide sequences of VP1. However, serotyping of RV based on alignment-based phylogeny is a multi-step process, which needs to be repeated every time a new isolate is sequenced. In view of the growing need for serotyping of RV, an alignment-free method based on "return time distribution" (RTD) of amino acid residues in VP1 protein has been developed and implemented in the form of a web server titled RV-Typer. RV-Typer accepts nucleotide or protein sequences as an input and computes return times of di-peptides (k = 2) to assign serotypes. The RV-Typer performs with 100% sensitivity and specificity. It is significantly faster than alignment-based methods. The web server is available at http://bioinfo.net.in/RV-Typer/home.html.
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Affiliation(s)
- Pandurang S. Kolekar
- Bioinformatics Centre, Savitribai Phule Pune University (formerly University of Pune), Pune, 411 007, India
| | - Vaishali P. Waman
- Bioinformatics Centre, Savitribai Phule Pune University (formerly University of Pune), Pune, 411 007, India
| | - Mohan M. Kale
- Department of Statistics, Savitribai Phule Pune University (formerly University of Pune), Pune, 411 007, India
| | - Urmila Kulkarni-Kale
- Bioinformatics Centre, Savitribai Phule Pune University (formerly University of Pune), Pune, 411 007, India
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48
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Royston L, Tapparel C. Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC. Viruses 2016; 8:E16. [PMID: 26761027 PMCID: PMC4728576 DOI: 10.3390/v8010016] [Citation(s) in RCA: 110] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Revised: 12/09/2015] [Accepted: 12/28/2015] [Indexed: 12/21/2022] Open
Abstract
Rhinoviruses (RVs) and respiratory enteroviruses (EVs) are leading causes of upper respiratory tract infections and among the most frequent infectious agents in humans worldwide. Both are classified in the Enterovirus genus within the Picornaviridae family and they have been assigned to seven distinct species, RV-A, B, C and EV-A, B, C, D. As viral infections of public health significance, they represent an important financial burden on health systems worldwide. However, the lack of efficient antiviral treatment or vaccines against these highly prevalent pathogens prevents an effective management of RV-related diseases. Current advances in molecular diagnostic techniques have revealed the presence of RV in the lower respiratory tract and its role in lower airway diseases is increasingly reported. In addition to an established etiological role in the common cold, these viruses demonstrate an unexpected capacity to spread to other body sites under certain conditions. Some of these viruses have received particular attention recently, such as EV-D68 that caused a large outbreak of respiratory illness in 2014, respiratory EVs from species C, or viruses within the newly-discovered RV-C species. This review provides an update of the latest findings on clinical and fundamental aspects of RV and respiratory EV, including a summary of basic knowledge of their biology.
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Affiliation(s)
- Léna Royston
- University of Geneva Faculty of Medicine, 1 Rue Michel-Servet, 1205 Geneva, Switzerland.
- Laboratory of Virology, Division of Infectious Diseases, University of Geneva Hospitals, 4 Rue Gabrielle Perret-Gentil, 1211 Geneva 14, Switzerland.
| | - Caroline Tapparel
- University of Geneva Faculty of Medicine, 1 Rue Michel-Servet, 1205 Geneva, Switzerland.
- Laboratory of Virology, Division of Infectious Diseases, University of Geneva Hospitals, 4 Rue Gabrielle Perret-Gentil, 1211 Geneva 14, Switzerland.
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L'Huillier AG, Kaiser L, Petty TJ, Kilowoko M, Kyungu E, Hongoa P, Vieille G, Turin L, Genton B, D'Acremont V, Tapparel C. Molecular Epidemiology of Human Rhinoviruses and Enteroviruses Highlights Their Diversity in Sub-Saharan Africa. Viruses 2015; 7:6412-23. [PMID: 26670243 PMCID: PMC4690871 DOI: 10.3390/v7122948] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Revised: 11/16/2015] [Accepted: 11/19/2015] [Indexed: 11/16/2022] Open
Abstract
Human rhinoviruses (HRVs) and enteroviruses (HEVs) belong to the Enterovirus genus and are the most frequent cause of infection worldwide, but data on their molecular epidemiology in Africa are scarce. To understand HRV and HEV molecular epidemiology in this setting, we enrolled febrile pediatric patients participating in a large prospective cohort assessing the causes of fever in Tanzanian children. Naso/oropharyngeal swabs were systematically collected and tested by real-time RT-PCR for HRV and HEV. Viruses from positive samples were sequenced and phylogenetic analyses were then applied to highlight the HRV and HEV types as well as recombinant or divergent strains. Thirty-eight percent (378/1005) of the enrolled children harboured an HRV or HEV infection. Although some types were predominant, many distinct types were co-circulating, including a vaccinal poliovirus, HEV-A71 and HEV-D68. Three HRV-A recombinants were identified: HRV-A36/HRV-A67, HRV-A12/HRV-A67 and HRV-A96/HRV-A61. Four divergent HRV strains were also identified: one HRV-B strain and three HRV-C strains. This is the first prospective study focused on HRV and HEV molecular epidemiology in sub-Saharan Africa. This systematic and thorough large screening with careful clinical data management confirms the wide genomic diversity of these viruses, brings new insights about their evolution and provides data about associated symptoms.
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Affiliation(s)
- Arnaud G L'Huillier
- Geneva University Hospitals and Medical School, 4 rue Gabrielle-Perret-Gentil, 1211 Geneva 14, Switzerland.
| | - Laurent Kaiser
- Geneva University Hospitals and Medical School, 4 rue Gabrielle-Perret-Gentil, 1211 Geneva 14, Switzerland.
| | - Tom J Petty
- Swiss Institute of Bioinformatics, Centre Medical Universitraire, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland.
| | - Mary Kilowoko
- Amana Regional Referral Hospital, PO box 25411, Dar es Salaam TZ-02, United Republic of Tanzania.
| | - Esther Kyungu
- St-Francis Hospital, PO box 73, Ifakara TZ-16, United Republic of Tanzania.
| | - Philipina Hongoa
- St-Francis Hospital, PO box 73, Ifakara TZ-16, United Republic of Tanzania.
| | - Gaël Vieille
- Geneva University Hospitals and Medical School, 4 rue Gabrielle-Perret-Gentil, 1211 Geneva 14, Switzerland.
| | - Lara Turin
- Geneva University Hospitals and Medical School, 4 rue Gabrielle-Perret-Gentil, 1211 Geneva 14, Switzerland.
| | - Blaise Genton
- Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel 4051, Switzerland.
- Centre Hospitalier Universitaire Vaudois, 21 rue du Bugnon, Lausanne 1011, Switzerland.
| | - Valérie D'Acremont
- Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel 4051, Switzerland.
- Centre Hospitalier Universitaire Vaudois, 21 rue du Bugnon, Lausanne 1011, Switzerland.
| | - Caroline Tapparel
- Geneva University Hospitals and Medical School, 4 rue Gabrielle-Perret-Gentil, 1211 Geneva 14, Switzerland.
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50
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Kim H, Kim K, Kwon T, Kim DW, Kim SS, Kim YJ. Secondary structure conservation of the stem-loop IV sub-domain of internal ribosomal entry sites in human rhinovirus clinical isolates. Int J Infect Dis 2015; 41:21-8. [PMID: 26518063 DOI: 10.1016/j.ijid.2015.10.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Revised: 10/17/2015] [Accepted: 10/21/2015] [Indexed: 01/19/2023] Open
Abstract
OBJECTIVES The aim of this study was to investigate the genetic diversity in the stem-loop (SL) IV sub-domain of the human rhinovirus (HRV) internal ribosomal entry site (IRES), which plays key roles in the initiation of viral translation by host protein interaction. METHODS The primary SL-IV sequences of 194 HRVs, consisting of 97 reference strains and 97 clinical isolates, including the IRES sub-domains SL-IVa, SL-IVb, SL-IVc, and SL-IVd, were analyzed using Lasergene, MEGA 4, and WebLogo. Additionally, secondary structures of SL-IV were predicted and classified by RNAfold and CentroidHomfold-LAST. RESULTS The predicted secondary structures of SL-IV showed variations in the position of bulbs, size of the loop, and length of stems. SL-IVc had the most highly conserved nucleotide sequence, with structures classified into two groups by the location of the poly(C) loop. Of the SL-IV sequences analyzed, 74 (79.56%) were classified in the major group and 19 (20.44%) in the minor group. Thirteen compensatory substitution pairs of SL-IVc contributed to maintaining the stem structure. CONCLUSIONS This study showed that the IRES secondary structures of a large number of reference and clinical HRVs were highly conserved, with several compensatory substitutions. It is expected that these results will facilitate investigations into HRV function based on IRES secondary structures.
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Affiliation(s)
- Hak Kim
- Division of Respiratory Viruses, Center for Infectious Diseases, Korea National Institute of Health, Cheongju-si, Chungbuk, 363-951, Republic of Korea; Department of Biotechnology, Catholic University of Korea, Bucheon-si, Gyeonggi-do, 420-743, Republic of Korea
| | - Kisoon Kim
- Division of Influenza Virus, Center for Infectious Diseases, Korea National Institute of Health, Cheongju-si, Chungbuk, 363-951, Republic of Korea
| | - Taesoo Kwon
- Division of Biosafety Evaluation and Control, Korea National Institute of Health, Cheongju-si, Chungbuk, 363-951, Republic of Korea
| | - Dae-Won Kim
- Division of Biosafety Evaluation and Control, Korea National Institute of Health, Cheongju-si, Chungbuk, 363-951, Republic of Korea
| | - Sung Soon Kim
- Division of Respiratory Viruses, Center for Infectious Diseases, Korea National Institute of Health, Cheongju-si, Chungbuk, 363-951, Republic of Korea
| | - You-Jin Kim
- Division of Respiratory Viruses, Center for Infectious Diseases, Korea National Institute of Health, Cheongju-si, Chungbuk, 363-951, Republic of Korea.
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