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Monamele CG, Njankouo RM, Yogne CN, Essengue LLM, Bilounga CN, Tsafack DT, Njifon HLM, Tamoufe U, Perraut R, Njouom R. Investigation of influenza A of pandemic potential and MERS-Coronavirus in humans in Cameroon. BMC Res Notes 2025; 18:133. [PMID: 40165265 PMCID: PMC11959992 DOI: 10.1186/s13104-025-07179-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 03/11/2025] [Indexed: 04/02/2025] Open
Abstract
OBJECTIVE According to the World Health Organization, surveillance for respiratory viruses with pandemic potential should be included in routine surveillance to be on alert for zoonotic transmission. This study reports on data from the surveillance of influenza A/H5, influenza A/H7 and MERS-Coronavirus in Cameroon. RESULTS A total of 855 participants were enrolled. Of these, 11.7% were positive for influenza A and none were positive for influenza A/H5, A/H7 and MERS-Coronavirus. Most participants (77.1%) were enrolled within 5 days of illness onset and the younger population under 2 years of age (31.4%) was the most represented. In terms of clinical manifestations, the majority had flu-like symptoms including fever, cough, rhinorrhoea, asthenia, shortness of breath, noisy breathing and headache. These results are important to fill the knowledge gap on the epidemiology of influenza A/H5, A/H7 and MERS-Coronavirus in humans, for which information is lacking in several countries.
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Affiliation(s)
- Chavely Gwladys Monamele
- Virology Service, Centre Pasteur of Cameroon, PO Box 1274, Yaounde, Cameroon
- Faculty of Health Sciences, University of Buea, PO Box 63, Buea, Cameroon
| | | | | | | | - Chanceline Ndongo Bilounga
- Department for the Control of Diseases, Epidemics and Pandemics (DLMEP), Ministry of Public Health, Yaounde, Cameroon
- Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon
| | - Desmon Toutou Tsafack
- Virology Service, Centre Pasteur of Cameroon, PO Box 1274, Yaounde, Cameroon
- Department of Biochemistry, University of Douala, Douala, Cameroon
| | | | | | - Ronald Perraut
- Garoua Annex, Centre Pasteur of Cameroon, Garoua, Cameroon
| | - Richard Njouom
- Virology Service, Centre Pasteur of Cameroon, PO Box 1274, Yaounde, Cameroon.
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Bia P, Losardo M, Manna A, Brusaferro S, Privitera GP, Vincentelli AS. Selected microwave irradiation effectively inactivates airborne avian influenza A(H5N1) virus. Sci Rep 2025; 15:2021. [PMID: 39814783 PMCID: PMC11735811 DOI: 10.1038/s41598-025-85376-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Accepted: 01/02/2025] [Indexed: 01/18/2025] Open
Abstract
The highly pathogenic avian influenza A(H5N1) virus threatens animal and human health globally. Innovative strategies are crucial for mitigating risks associated with airborne transmission and preventing outbreaks. In this study, we sought to investigate the efficacy of microwave inactivation against aerosolized A(H5N1) virus by identifying the optimal frequency band for a 10-min exposure and evaluating the impact of varying exposure times on virus inactivation. A(H5N1) was aerosolized and exposed to various microwave frequencies ranging from 8 to 16 GHz for a duration of 10 min. Viral titers were quantified using TCID50, and inactivation was assessed by comparing irradiated samples to controls. The 11-13 GHz band yielded the highest inactivation, with an average 89% mean reduction in A(H5N1) titer, particularly within the 11-12 GHz range, which exhibited peak efficacy. Based on the overall results, the optimal frequency band (8-12 GHz) was further tested with exposure durations of 1, 3, and 5 min. Inactivation was time-dependent, with a 5-minute exposure resulting in a 94% mean reduction, compared to 58% and 48% for 3- and 1-minute exposures, respectively. We conclude that optimized microwave emitters in high-risk environments like poultry farms and veterinary clinics could offer a novel, non-chemical approach to mitigating avian influenza spread and outbreaks.
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Affiliation(s)
- Pietro Bia
- Elettronica S.p.A, Via Tiburtina Valeria, Km 13.700, Rome, 00131, Italy.
| | | | - Antonio Manna
- Elettronica S.p.A, Via Tiburtina Valeria, Km 13.700, Rome, 00131, Italy
| | - Silvio Brusaferro
- Department of Medicine, University of Udine, Udine, Italy
- e4life srl, Via Giorgio Vasari 4, Rome, 00196, Italy
| | - Gaetano P Privitera
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
- e4life srl, Via Giorgio Vasari 4, Rome, 00196, Italy
| | - Alberto Sangiovanni Vincentelli
- The Edgar L. and Harold H. Buttner Chair of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA, USA
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Hassman RL, McCabe IMH, Smith KM, Allen LJS. Stochastic Models of Zoonotic Avian Influenza with Multiple Hosts, Environmental Transmission, and Migration in the Natural Reservoir. Bull Math Biol 2024; 87:14. [PMID: 39674959 DOI: 10.1007/s11538-024-01396-9] [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: 07/11/2024] [Accepted: 12/04/2024] [Indexed: 12/17/2024]
Abstract
Avian influenza virus type A causes an infectious disease that circulates among wild bird populations and regularly spills over into domesticated animals, such as poultry and swine. As the virus replicates in these intermediate hosts, mutations occur, increasing the likelihood of emergence of a new variant with greater transmission to humans and a potential threat to public health. Prior models for spread of avian influenza have included some combinations of the following components: multi-host populations, spillover into humans, environmental transmission, seasonality, and migration. We develop an ordinary differential equation (ODE) model for spread of a low pathogenic avian influenza virus that combines all of these factors, and we translate this into a stochastic continuous-time Markov chain model. Linearization of the ODE near the disease-free solution leads to the basic reproduction number R 0 , a threshold for disease extinction in both the ODE and Markov chain. The linearized Markov chain leads to a branching process approximation which provides an estimate for probability of disease extinction, i.e., probability no major disease outbreak in the multi-host system. The probability of disease extinction depends on the time and the population into which infection is introduced and reflects the seasonality inherent in the system. Some of the most sensitive parameters to model outcomes include wild bird recovery and environmental transmission. We find that migratory wild birds can drive infection numbers in other populations even when transmission parameters for those populations are low, and that environmental transmission can be a significant driver of infections.
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Affiliation(s)
- Rowan L Hassman
- Department of Mathematics, Bates College, Lewiston, ME, 04240, USA.
| | - Iona M H McCabe
- Department of Mathematics, University of California, Santa Barbara, CA, 93106, USA
| | - Kaia M Smith
- Department of Mathematics, University of California, Davis, CA, 95616, USA
| | - Linda J S Allen
- Department of Mathematics and Statistics, Texas Tech University, Lubbock, TX, 79409, USA
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Bhatia B, Sonar S, Khan S, Bhattacharya J. Pandemic-Proofing: Intercepting Zoonotic Spillover Events. Pathogens 2024; 13:1067. [PMID: 39770327 PMCID: PMC11728701 DOI: 10.3390/pathogens13121067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 11/04/2024] [Accepted: 11/04/2024] [Indexed: 01/12/2025] Open
Abstract
Zoonotic spillover events pose a significant and growing threat to global health. By focusing on preventing these cross-species transmissions, we can significantly mitigate pandemic risks. This review aims to analyze the mechanisms of zoonotic spillover events, identify key risk factors, and propose evidence-based prevention strategies to reduce future pandemic threats. Through a comprehensive literature review and analysis of major databases including PubMed, Web of Science, and Scopus from 1960-2024, we examined documented spillover events, their outcomes, and intervention strategies. This article emphasizes that targeting the root cause-the spillover event itself-is key to averting future pandemics. By analyzing historical and contemporary outbreaks, we extract crucial insights into the dynamics of zoonotic transmission. Factors underlying these events include increased human-animal contact due to habitat encroachment, agricultural intensification, and wildlife trade. Climate change, global travel, and inadequate healthcare infrastructure exacerbate risks. The diversity of potential viral reservoirs and rapid viral evolution present major challenges for prediction and prevention. Solutions include enhancing surveillance of wildlife populations, improving biosecurity measures, investing in diagnostic capabilities, and promoting sustainable wildlife management. A "One Health" approach integrating human, animal, and environmental health is crucial. Predictive modelling, international cooperation, and public education are key strategies. Developing pre-exposure prophylactics and post-exposure treatments is essential for mitigating outbreaks. While obstacles remain, advances in genomics and ecological modelling offer hope. A proactive, comprehensive approach addressing the root causes of spillover events is vital for safeguarding global health against future pandemics.
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Affiliation(s)
- Bharti Bhatia
- Molecular and Translational Virology, Centre for Virus Research, Vaccines and Therapeutics, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad 121001, India
| | - Sudipta Sonar
- Molecular and Translational Virology, Centre for Virus Research, Vaccines and Therapeutics, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad 121001, India
| | - Seema Khan
- Molecular and Translational Virology, Centre for Virus Research, Vaccines and Therapeutics, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad 121001, India
| | - Jayanta Bhattacharya
- Molecular and Translational Virology, Centre for Virus Research, Vaccines and Therapeutics, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad 121001, India
- Antibody Translational Research Program, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad 121001, India
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5
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Li W, Gao M, Hao Y, Chi H, Yu J. Beneficial effect of sequential treatment with high-dose steroids and short-course oral glucocorticoids in patients with severe influenza virus-associated pneumonia. Sci Rep 2024; 14:25023. [PMID: 39443650 PMCID: PMC11499680 DOI: 10.1038/s41598-024-76400-2] [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: 06/21/2024] [Accepted: 10/14/2024] [Indexed: 10/25/2024] Open
Abstract
Accumulating evidence supports that glucocorticoid treatment for viral pneumonia (VPA) can shorten the disease course and improve survival. However, currently, the use of glucocorticoids in treating VPA remains controversial. Moreover, a unified standard for the dosage and duration of glucocorticoid therapy has not been presented in published articles. A retrospective analysis was conducted in patients who were hospitalized for severe influenza virus-associated pneumonia, and they received sequential treatment with high-dose glucocorticoids and short-course oral glucocorticoids. Patients were followed up for 3 months. A total of 11 patients were included in the study (average age 56 years). There was no gender difference, but age and underlying diseases could be risk factors for severe influenza virus-associated pneumonia. The types of viruses causing pneumonia included influenza A/B. The main clinical symptoms of patients were fever, cough, sputum production, and dyspnea. Chest computed tomography showed multiple ground-glass shadows in the lobes, and the presence of bacterial and fungal infections was accompanied by consolidation shadows. After glucocorticoid therapy, the symptoms improved. None of the patients underwent tracheal intubation, and all survived. After a 3-month follow-up, lung CT absorption in all patients had reached more than 80%, and lung imaging absorption in 20% patients was complete. No serious complications occurred in any of the patients. Sequential treatment with high-dose steroids and short-course oral glucocorticoids may be helpful for reducing the tracheal intubation rate and mortality rate in patients with severe influenza virus-associated pneumonia. Additionally, short-course oral glucocorticoids may reduce pulmonary fibrosis in patients with severe influenza virus-associated pneumonia without any serious complications.
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Affiliation(s)
- Wei Li
- Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Mingyue Gao
- Department of Nuclear Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Yuqiu Hao
- Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Hao Chi
- Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Jinyan Yu
- Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China.
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Dai J, Zhao J, Xia J, Zhang P, Ding Y, Li Q, Hou M, Xiong X, Jian Q, Liu Y, Liu G. Phylogenetic and mutational analysis of H10N3 avian influenza A virus in China: potential threats to human health. Front Cell Infect Microbiol 2024; 14:1433661. [PMID: 38979510 PMCID: PMC11228180 DOI: 10.3389/fcimb.2024.1433661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Accepted: 06/07/2024] [Indexed: 07/10/2024] Open
Abstract
In recent years, the avian influenza virus has emerged as a significant threat to both human and public health. This study focuses on a patient infected with the H10N3 subtype of avian influenza virus, admitted to the Third People's Hospital of Kunming City on March 6, 2024. Metagenomic RNA sequencing and polymerase chain reaction (PCR) analysis were conducted on the patient's sputum, confirming the H10N3 infection. The patient presented severe pneumonia symptoms such as fever, expectoration, chest tightness, shortness of breath, and cough. Phylogenetic analysis of the Haemagglutinin (HA) and neuraminidase (NA) genes of the virus showed that the virus was most closely related to a case of human infection with the H10N3 subtype of avian influenza virus found in Zhejiang Province, China. Analysis of amino acid mutation sites identified four mutations potentially hazardous to human health. Consequently, this underscores the importance of continuous and vigilant monitoring of the dynamics surrounding the H10N3 subtype of avian influenza virus, utilizing advanced genomic surveillance techniques.
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Affiliation(s)
- Jingyi Dai
- Department of Public Laboratory, The Third People's Hospital of Kunming City/Infectious Disease Clinical Medical Center of Yunnan Province, Kunming, Yunnan, China
| | - Jun Zhao
- School of Public Health, Hubei University of Medicine, Shiyan, China
| | - Jiawei Xia
- Department of Public Laboratory, The Third People's Hospital of Kunming City/Infectious Disease Clinical Medical Center of Yunnan Province, Kunming, Yunnan, China
| | - Pei Zhang
- Department of Public Laboratory, The Third People's Hospital of Kunming City/Infectious Disease Clinical Medical Center of Yunnan Province, Kunming, Yunnan, China
| | - Yadi Ding
- Department of Public Laboratory, The Third People's Hospital of Kunming City/Infectious Disease Clinical Medical Center of Yunnan Province, Kunming, Yunnan, China
| | - Qiujing Li
- Department of Public Laboratory, The Third People's Hospital of Kunming City/Infectious Disease Clinical Medical Center of Yunnan Province, Kunming, Yunnan, China
| | - Min Hou
- Department of Microbiological Laboratory, Kunming City Center for Disease Control and Prevention, Kunming, China
| | - Xianhui Xiong
- Department of Microbiological Laboratory, Kunming City Center for Disease Control and Prevention, Kunming, China
| | - Qianqi Jian
- Department of Microbiological Laboratory, Kunming City Center for Disease Control and Prevention, Kunming, China
| | - Yanyan Liu
- Department of Microbiological Laboratory, Kunming City Center for Disease Control and Prevention, Kunming, China
| | - Guiming Liu
- Department of Public Laboratory, The Third People's Hospital of Kunming City/Infectious Disease Clinical Medical Center of Yunnan Province, Kunming, Yunnan, China
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Hohensee L, Scheibner D, Schäfer A, Shelton H, Mettenleiter TC, Breithaupt A, Dorhoi A, Abdelwhab EM, Blohm U. The role of PB1-F2 in adaptation of high pathogenicity avian influenza virus H7N7 in chickens. Vet Res 2024; 55:5. [PMID: 38173025 PMCID: PMC10765749 DOI: 10.1186/s13567-023-01257-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 11/29/2023] [Indexed: 01/05/2024] Open
Abstract
Avian influenza viruses (AIV) of the H7N7 subtype are enzootic in the wild bird reservoir in Europe, cause infections in poultry, and have sporadically infected humans. The non-structural protein PB1-F2 is encoded in a second open frame in the polymerase segment PB1 and its sequence varies with the host of origin. While mammalian isolates predominantly carry truncated forms, avian isolates typically express full-length PB1-F2. PB1-F2 is a virulence factor of influenza viruses in mammals. It modulates the host immune response, causing immunopathology and increases pro-inflammatory responses. The role of full-length PB1-F2 in IAV pathogenesis as well as its impact on virus adaptation and virulence in poultry remains enigmatic. Here, we characterised recombinant high pathogenicity AIV (HPAIV) H7N7 expressing or lacking PB1-F2 in vitro and in vivo in chickens. In vitro, full-length PB1-F2 modulated viability of infected chicken fibroblasts by limiting apoptosis. In chickens, PB1-F2 promoted gastrointestinal tropism, as demonstrated by enhanced viral replication in the gut and increased cloacal shedding. PB1-F2's effects on cellular immunity however were marginal. Overall, chickens infected with full-length PB1-F2 virus survived for shorter periods, indicating that PB1-F2 is also a virulence factor in bird-adapted viruses.
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Affiliation(s)
- Luise Hohensee
- Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493, Greifswald, Insel Riems, Germany
- Infection Pathogenesis, TUM School of Life Sciences, Technische Universität München, 85354, Freising, Germany
| | - David Scheibner
- Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493, Greifswald, Insel Riems, Germany
| | - Alexander Schäfer
- Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493, Greifswald, Insel Riems, Germany
| | - Holly Shelton
- The Pirbright Institute, Pirbright, Ash Road, Surrey, GU24 0NF, UK
| | - Thomas C Mettenleiter
- Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493, Greifswald, Insel Riems, Germany
| | - Angele Breithaupt
- Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493, Greifswald, Insel Riems, Germany
| | - Anca Dorhoi
- Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493, Greifswald, Insel Riems, Germany
| | - Elsayed M Abdelwhab
- Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493, Greifswald, Insel Riems, Germany
| | - Ulrike Blohm
- Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493, Greifswald, Insel Riems, Germany.
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8
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Chiu KHY, Sridhar S, Yuen KY. Preparation for the next pandemic: challenges in strengthening surveillance. Emerg Microbes Infect 2023; 12:2240441. [PMID: 37474466 PMCID: PMC10478602 DOI: 10.1080/22221751.2023.2240441] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Revised: 07/18/2023] [Accepted: 07/19/2023] [Indexed: 07/22/2023]
Abstract
The devastating Coronavirus Disease 2019 (COVID-19) pandemic indicates that early detection of candidates with pandemic potential is vital. However, comprehensive metagenomic sequencing of the total microbiome is not practical due to the astronomical and rapidly evolving numbers and species of micro-organisms. Analysis of previous pandemics suggests that an increase in human-animal interactions, changes in animal and arthropod distribution due to climate change and deforestation, continuous mutations and interspecies jumping of RNA viruses, and frequent travels are important factors driving pandemic emergence. Besides measures mitigating these factors, surveillance at human-animal interfaces targeting animals with unusual tolerance to viral infections, sick heathcare workers, and workers at high biosafety level laboratories is crucial. Surveillance of sick travellers is important when alerted by an early warning system of a suspected outbreak due to unknown agents. These samples should be screened by multiplex nucleic acid amplification and subsequent unbiased next-generation sequencing. Novel viruses should be isolated in routine cell cultures, complemented by organoid cultures, and then tested in animal models for interspecies transmission potential. Potential agents are candidates for designing rapid diagnostics, therapeutics, and vaccines. For early detection of outbreaks, there are advantages in using event-based surveillance and artificial intelligence (AI), but high background noise and censorship are possible drawbacks. These systems are likely useful if they channel reliable information from frontline healthcare or veterinary workers and large international gatherings. Furthermore, sufficient regulation of high biosafety level laboratories, and stockpiling of broad spectrum antiviral drugs, vaccines, and personal protective equipment are indicated for pandemic preparedness.
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Affiliation(s)
- Kelvin Hei-Yeung Chiu
- Department of Microbiology, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China
| | - Siddharth Sridhar
- State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
| | - Kwok-Yung Yuen
- State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
- Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
- Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, People’s Republic of China
- Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, People's Republic of China
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Miller A, Reddy PJ, Randolph D, Breton PP, Dickinson P, Hyde MJ. A Rare Case of Community-Acquired Pneumonia Only Presenting With Diarrhea, Abdominal Pain, and Fever: A Case Report. Cureus 2023; 15:e44368. [PMID: 37779758 PMCID: PMC10540503 DOI: 10.7759/cureus.44368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/29/2023] [Indexed: 10/03/2023] Open
Abstract
Legionnaires' disease is an atypical pneumonia caused by Legionella pneumophila (L. pneumophila) pneumonia that features slow onset, nonproductive cough, fatigue, headache, sore throat, myalgias, and malaise. It can be difficult to diagnose, as it presents with extrapulmonary symptoms, and delay in treatment can be fatal. Here, we present the case of a previously healthy 32-year-old Caucasian male with Legionnaires disease who only presented to the clinic with abdominal pain and diarrhea. The patient did not have any pulmonary symptoms at the initial presentation. This presentation did not fit the diagnostic tools available for Legionnaires' disease, including a validated clinical prediction rule, which ruled out L. pneumophila infection with a sensitivity of 97% and a negative predictive value of 99.4%. Due to the complaint of abdominal pain, a flat/upright abdominal X-ray was ordered, which includes a chest X-ray. Upon analyzing the chest X-ray, a right lower lobe consolidation was identified, prompting an L. pneumophila urinary test to be added to the lab orders. This case represents the difficulties in diagnosing Legionnaires' disease due to the diverse clinical complexities of presentations, which may solely involve abdominal complaints.
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Affiliation(s)
- Austin Miller
- Medicine, Alabama College of Osteopathic Medicine, Dothan, USA
| | - Punuru J Reddy
- Internal Medicine, Decatur Morgan Hospital, Decatur, USA
| | - Derrick Randolph
- Family and Community Medicine, Decatur Morgan Hospital, Decatur, USA
| | - Philip P Breton
- Medicine, Alabama College of Osteopathic Medicine, Dothan, USA
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10
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Docherty CAH, Fernando AJ, Rosli S, Lam M, Dolle RE, Navia MA, Farquhar R, La France D, Tate MD, Murphy CK, Rossi AG, Mansell A. A novel dual NLRP1 and NLRP3 inflammasome inhibitor for the treatment of inflammatory diseases. Clin Transl Immunology 2023; 12:e1455. [PMID: 37360982 PMCID: PMC10288073 DOI: 10.1002/cti2.1455] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Revised: 05/14/2023] [Accepted: 06/06/2023] [Indexed: 06/28/2023] Open
Abstract
Objectives Inflammasomes induce maturation of the inflammatory cytokines IL-1β and IL-18, whose activity is associated with the pathophysiology of a wide range of infectious and inflammatory diseases. As validated therapeutic targets for the treatment of acute and chronic inflammatory diseases, there has been intense interest in developing small-molecule inhibitors to target inflammasome activity and reduce disease-associated inflammatory burden. Methods We examined the therapeutic potential of a novel small-molecule inhibitor, and associated derivatives, termed ADS032 to target and reduce inflammasome-mediated inflammation in vivo. In vitro, we characterised ADS032 function, target engagement and specificity. Results We describe ADS032 as the first dual NLRP1 and NLRP3 inhibitor. ADS032 is a rapid, reversible and stable inflammasome inhibitor that directly binds both NLRP1 and NLRP3, reducing secretion and maturation of IL-1β in human-derived macrophages and bronchial epithelial cells in response to the activation of NLPR1 and NLRP3. ADS032 also reduced NLRP3-induced ASC speck formation, indicative of targeting inflammasome formation. In vivo, ADS032 reduced IL-1β and TNF-α levels in the serum of mice challenged i.p. with LPS and reduced pulmonary inflammation in an acute model of lung silicosis. Critically, ADS032 protected mice from lethal influenza A virus challenge, displayed increased survival and reduced pulmonary inflammation. Conclusion ADS032 is the first described dual inflammasome inhibitor and a potential therapeutic to treat both NLRP1- and NLRP3-associated inflammatory diseases and also constitutes a novel tool that allows examination of the role of NLRP1 in human disease.
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Affiliation(s)
- Callum AH Docherty
- Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchClaytonVICAustralia
- Department of Molecular and Translational SciencesMonash UniversityClaytonVICAustralia
| | - Anuruddika J Fernando
- University of Edinburgh Centre for Inflammation ResearchQueen's Medical Research Institute, Edinburgh BioQuarterEdinburghUK
| | - Sarah Rosli
- Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchClaytonVICAustralia
- Department of Molecular and Translational SciencesMonash UniversityClaytonVICAustralia
| | - Maggie Lam
- Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchClaytonVICAustralia
- Department of Molecular and Translational SciencesMonash UniversityClaytonVICAustralia
| | - Roland E Dolle
- Department of Biochemistry and Molecular BiophysicsWashington University School of MedicineSt. LouisMOUSA
| | | | | | | | - Michelle D Tate
- Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchClaytonVICAustralia
- Department of Molecular and Translational SciencesMonash UniversityClaytonVICAustralia
| | | | - Adriano G Rossi
- University of Edinburgh Centre for Inflammation ResearchQueen's Medical Research Institute, Edinburgh BioQuarterEdinburghUK
| | - Ashley Mansell
- Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchClaytonVICAustralia
- Department of Molecular and Translational SciencesMonash UniversityClaytonVICAustralia
- Adiso TherapeuticsConcordMAUSA
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Pasitka L, Cohen M, Ehrlich A, Gildor B, Reuveni E, Ayyash M, Wissotsky G, Herscovici A, Kaminker R, Niv A, Bitcover R, Dadia O, Rudik A, Voloschin A, Shimoni M, Cinnamon Y, Nahmias Y. Spontaneous immortalization of chicken fibroblasts generates stable, high-yield cell lines for serum-free production of cultured meat. NATURE FOOD 2023; 4:35-50. [PMID: 37118574 DOI: 10.1038/s43016-022-00658-w] [Citation(s) in RCA: 57] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 11/03/2022] [Indexed: 04/30/2023]
Abstract
Cellular agriculture could meet growing demand for animal products, but yields are typically low and regulatory bodies restrict genetic modification for cultured meat production. Here we demonstrate the spontaneous immortalization and genetic stability of fibroblasts derived from several chicken breeds. Cell lines were adapted to grow as single-cell suspensions using serum-free culture medium, reaching densities of 108 × 106 cells per ml in continuous culture, corresponding to yields of 36% w/v. We show that lecithin activates peroxisome proliferator-activated receptor gamma (PPARγ), inducing adipogenesis in immortalized fibroblasts. Blending cultured adipocyte-like cells with extruded soy protein, formed chicken strips in which texture was supported by animal and plant proteins while aroma and flavour were driven by cultured animal fat. Visual and sensory analysis graded the product 4.5/5.0, with 85% of participants extremely likely to replace their food choice with this cultured meat product. Immortalization without genetic modification and high-yield manufacturing are critical for the market realization of cultured meat.
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Affiliation(s)
- L Pasitka
- Grass Center for Bioengineering, Benin School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - M Cohen
- Grass Center for Bioengineering, Benin School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel
- Department of Cell and Developmental Biology, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - A Ehrlich
- Grass Center for Bioengineering, Benin School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel
| | | | | | - M Ayyash
- Grass Center for Bioengineering, Benin School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel
- Believer Meats, Rehovot, Israel
| | | | | | | | - A Niv
- Believer Meats, Rehovot, Israel
| | | | - O Dadia
- Believer Meats, Rehovot, Israel
| | - A Rudik
- Believer Meats, Rehovot, Israel
| | | | | | - Y Cinnamon
- Institute of Animal Science, Agricultural Research Organization, The Volcani Center, Bet Dagan, Israel
| | - Y Nahmias
- Grass Center for Bioengineering, Benin School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
- Department of Cell and Developmental Biology, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
- Believer Meats, Rehovot, Israel.
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12
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Noisumdaeng P, Phadungsombat J, Weerated S, Wiriyarat W, Puthavathana P. Genetic evolution of hemagglutinin and neuraminidase genes of H5N1 highly pathogenic avian influenza viruses in Thailand. PeerJ 2022; 10:e14419. [PMID: 36518286 PMCID: PMC9744161 DOI: 10.7717/peerj.14419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 10/28/2022] [Indexed: 12/05/2022] Open
Abstract
Background Ongoing outbreaks of H5N1 highly pathogenic avian influenza (HPAI) viruses and the emergence of the genetic-related hemagglutinin (HA) gene of reassortant H5Nx viruses currently circulating in wild birds and poultries pose a great global public health concern. In this study, we comprehensively analyzed the genetic evolution of Thai H5N1 HA and neuraminidase (NA) genes between 2003 and 2010. The H5N1 Thailand virus clade 2.3.4 was also genetically compared to the currently circulating clade 2.3.4.4 of H5Nx viruses. Methods Full-length nucleotide sequences of 178 HA and 143 NA genes of H5N1 viruses circulating between 2003 and 2010 were phylogenetically analyzed using maximum likelihood (ML) phylogenetic construction. Bayesian phylogenetic trees were reconstructed using BEAST analysis with a Bayesian Markov chain Monte Carlo (MCMC) approach. The maximum clade credibility (MCC) tree was determined, and the time of the most recent common ancestor (tMRCA) was estimated. The H5N1 HA nucleotide sequences of clade 2.3.4 Thailand viruses were phylogenetically analyzed using ML phylogenetic tree construction and analyzed for nucleotide similarities with various subtypes of reassortant H5Nx HA clade 2.3.4.4. Results ML phylogenetic analysis revealed two distinct HA clades, clade 1 and clade 2.3.4, and two distinct NA groups within the corresponding H5 clade 1 viruses. Bayesian phylogenetic reconstruction for molecular clock suggested that the Thai H5N1 HA and NA emerged in 2001.87 (95% HPD: 2001.34-2002.49) and 2002.38 (95% HPD: 2001.99-2002.82), respectively, suggesting that the virus existed before it was first reported in 2004. The Thai H5N1 HA clade 2.3.4 was grouped into corresponding clades 2.3.4, 2.3.4.1, 2.3.4.2, and 2.3.4.3, and shared nucleotide similarities to reassortant H5Nx clade 2.3.4.4 ranged from 92.4-96.8%. Phylogenetic analysis revealed monophyletic H5Nx clade 2.3.4.4 evolved from H5N1 clade 2.3.4. Conclusion H5N1 viruses existed, and were presumably introduced and circulated in avian species in Thailand, before they were officially reported in 2004. HA and NA genes continuously evolved during circulation between 2004 and 2010. This study provides a better understanding of genetic evolution with respect to molecular epidemiology. Monitoring and surveillance of emerging variants/reassortants should be continued.
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Affiliation(s)
- Pirom Noisumdaeng
- Faculty of Public Health, Thammasat University, Khlong Luang, Pathum Thani, Thailand,Thammasat University Research Unit in Modern Microbiology and Public Health Genomics, Thammasat University, Khlong Luang, Pathum Thani, Thailand
| | - Juthamas Phadungsombat
- Mahidol-Osaka Center for Infectious Diseases (MOCID), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand,Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
| | - Sasrinakarn Weerated
- Faculty of Public Health, Thammasat University, Khlong Luang, Pathum Thani, Thailand
| | | | - Pilaipan Puthavathana
- Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand
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13
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Muraduzzaman AKM, Illing PT, Mifsud NA, Purcell AW. Understanding the Role of HLA Class I Molecules in the Immune Response to Influenza Infection and Rational Design of a Peptide-Based Vaccine. Viruses 2022; 14:2578. [PMID: 36423187 PMCID: PMC9695287 DOI: 10.3390/v14112578] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 11/04/2022] [Accepted: 11/18/2022] [Indexed: 11/23/2022] Open
Abstract
Influenza A virus is a respiratory pathogen that is responsible for regular epidemics and occasional pandemics that result in substantial damage to life and the economy. The yearly reformulation of trivalent or quadrivalent flu vaccines encompassing surface glycoproteins derived from the current circulating strains of the virus does not provide sufficient cross-protection against mismatched strains. Unlike the current vaccines that elicit a predominant humoral response, vaccines that induce CD8+ T cells have demonstrated a capacity to provide cross-protection against different influenza strains, including novel influenza viruses. Immunopeptidomics, the mass spectrometric identification of human-leukocyte-antigen (HLA)-bound peptides isolated from infected cells, has recently provided key insights into viral peptides that can serve as potential T cell epitopes. The critical elements required for a strong and long-living CD8+ T cell response are related to both HLA restriction and the immunogenicity of the viral peptide. This review examines the importance of HLA and the viral immunopeptidome for the design of a universal influenza T-cell-based vaccine.
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Affiliation(s)
| | | | - Nicole A. Mifsud
- Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia
| | - Anthony W. Purcell
- Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia
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14
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Kanaujia R, Bora I, Ratho RK, Thakur V, Mohi GK, Thakur P. Avian influenza revisited: concerns and constraints. Virusdisease 2022; 33:456-465. [PMID: 36320191 PMCID: PMC9614751 DOI: 10.1007/s13337-022-00800-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 10/15/2022] [Indexed: 12/05/2022] Open
Abstract
Avian influenza (AVI) is being known for its pandemic potential and devastating effects on poultry and birds. The AVI outbreaks in domesticated birds are of concern because the Low pathogenic avian influenza virus (LPAI) tends to evolve into a High pathogenic avian influenza virus (HPAI) resulting in the rapid spread and significant outbreak in poultries. The containment should be rapid and stringent precautions should be taken in handling the infected poultry cases or infected materials. In general, AVI viruses do not replicate efficiently in humans, indicating that transmitting these viruses to humans directly is a very rare preference. However, the HPAI ability to the cross-species barrier and infect humans has been known for H5N1 and H7N9. Recently, the world's first human case of transmission of the H5N8 strain from the avian species to humans has been documented. In this recent scenario, it is worth discussing the strain variations, disease severity, economic loss, and effective controlling strategies for controlling avian influenza.
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15
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Cui J, Cui P, Shi J, Fan W, Xing X, Gu W, Zhang Y, Zhang Y, Zeng X, Jiang Y, Chen P, Yang H, Chen Y, Liu J, Liu L, Tian G, Lu Y, Chen H, Li C, Deng G. Continued evolution of H6 avian influenza viruses isolated from farms in China between 2014 and 2018. Transbound Emerg Dis 2022; 69:2156-2172. [PMID: 34192815 DOI: 10.1111/tbed.14212] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 06/04/2021] [Accepted: 06/27/2021] [Indexed: 12/22/2022]
Abstract
H6 avian influenza virus (AIV) is one of the most prevalent AIV subtypes in the world. Our previous studies have demonstrated that H6 AIVs isolated from live poultry markets pose a potential threat to human health. In recent years, increasing number of H6 AIVs has been constantly isolated from poultry farms. In order to understand the biological characteristics of H6 AIVs in the context of farms, here, we analyzed the phylogenetic relationships, antigenicity, replication in mice and receptor binding properties of H6 AIVs isolated from farms in China between 2014 and 2018. Phylogenetic analysis showed that 19 different genotypes were formed among 20 representative H6 viruses. Notably, the internal genes of these H6 viruses exhibited complicated relationships with different subtypes of AIVs worldwide, indicating that these viruses are the products of complex and frequent reassortment events. Antigenic analysis revealed that 13 viruses tested were divided into three antigenic groups. 10 viruses examined could all replicate in the respiratory organs of infected mice without prior adaptation. Receptor binding analysis demonstrated that some of the H6 AIVs bound to both α-2, 3-linked glycans (avian-type receptor) and α-2, 6-linked glycans (human-type receptor), thereby posing a potential threat to human health. Together, these findings revealed the prevalence, complicated genetic evolution, diverse antigenicity, and dual receptor binding specificity of H6 AIVs in the settings of poultry farms, which emphasize the importance to continuously monitor the evolution and biological properties of H6 AIVs in nature.
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Affiliation(s)
- Jiaqi Cui
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, P. R. China
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, P. R. China
| | - Pengfei Cui
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, P. R. China
| | - Jianzhong Shi
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, P. R. China
| | - Weifeng Fan
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, P. R. China
| | - Xin Xing
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, P. R. China
| | - Wenli Gu
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, P. R. China
| | - Yuancheng Zhang
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, P. R. China
| | - Yaping Zhang
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, P. R. China
| | - Xianying Zeng
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, P. R. China
| | - Yongping Jiang
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, P. R. China
| | - Pucheng Chen
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, P. R. China
| | - Huanliang Yang
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, P. R. China
| | - Yan Chen
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, P. R. China
| | - Jinxiong Liu
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, P. R. China
| | - Liling Liu
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, P. R. China
| | - Guobin Tian
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, P. R. China
| | - Yixin Lu
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, P. R. China
| | - Hualan Chen
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, P. R. China
| | - Chengjun Li
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, P. R. China
| | - Guohua Deng
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, P. R. China
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16
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Aswad M, Hamza H, Pechkovsky A, Zikrach A, Popov T, Zohar Y, Shahar E, Louria-Hayon I. High-CBD Extract (CBD-X) Downregulates Cytokine Storm Systemically and Locally in Inflamed Lungs. Front Immunol 2022; 13:875546. [PMID: 35651623 PMCID: PMC9149302 DOI: 10.3389/fimmu.2022.875546] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 04/19/2022] [Indexed: 12/21/2022] Open
Abstract
Cytokine storm refers to the dysregulated production of inflammatory mediators leading to hyperinflammation. They are often detrimental, and worsen the severity of COVID-19 and other infectious or inflammatory diseases. Cannabinoids are known to have anti-inflammatory effects but their possible therapeutic value on cytokine storms has not been fully elucidated. In vivo and ex vivo studies were carried out to investigate the effects of high-THC and high-CBD extracts on cytokine production in immune cells. Significant differences between the extracts were observed. Subsequent experiments focusing on a specific high CBD extract (CBD-X) showed significant reductions in pro-inflammatory cytokines in human-derived PBMCs, neutrophils and T cells. In vivo mouse studies, using a systemically inflamed mouse model, showed reductions in pro-inflammatory cytokines TNFα and IL-1β and a concurrent increase in the anti-inflammatory cytokine IL-10 in response to CBD-X extract treatment. Lung inflammation, as in severe COVID-19 disease, is characterized by increased T-cell homing to the lungs. Our investigation revealed that CBD-X extract impaired T-cell migration induced by the chemoattractant SDF1. In addition, the phosphorylation levels of T cell receptor (TCR) signaling proteins Lck and Zap70 were significantly reduced, demonstrating an inhibitory effect on the early events downstream to TCR activation. In a lung inflamed mouse model, we observed a reduction in leukocytes including neutrophil migration to the lungs and decreased levels of IL-1β, MCP-1, IL-6 and TNFα, in response to the administration of the high-CBD extract. The results presented in this work offer that certain high-CBD extract has a high potential in the management of pathological conditions, in which the secretion of cytokines is dysregulated, as it is in severe COVID-19 disease or other infectious or inflammatory diseases.
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Affiliation(s)
- Miran Aswad
- Medical Cannabis Research and Innovation Center, Rambam Health Care Campus, Haifa, Israel
| | - Haya Hamza
- Medical Cannabis Research and Innovation Center, Rambam Health Care Campus, Haifa, Israel
| | - Antonina Pechkovsky
- Medical Cannabis Research and Innovation Center, Rambam Health Care Campus, Haifa, Israel
| | - Anastasiia Zikrach
- Medical Cannabis Research and Innovation Center, Rambam Health Care Campus, Haifa, Israel
| | - Tania Popov
- Medical Cannabis Research and Innovation Center, Rambam Health Care Campus, Haifa, Israel
| | - Yaniv Zohar
- Pathology Department, Rambam Health Care Campus, Haifa, Israel
| | - Eduardo Shahar
- Clinical Immunology Unit, Rambam Health Care Campus, Haifa, Israel
| | - Igal Louria-Hayon
- Medical Cannabis Research and Innovation Center, Rambam Health Care Campus, Haifa, Israel.,Clinical Research Institute at Rambam (CRIR), Rambam Health Care Campus, Haifa, Israel
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17
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Pathogenesis of pneumonia and acute lung injury. Clin Sci (Lond) 2022; 136:747-769. [PMID: 35621124 DOI: 10.1042/cs20210879] [Citation(s) in RCA: 161] [Impact Index Per Article: 53.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 04/29/2022] [Accepted: 05/09/2022] [Indexed: 12/15/2022]
Abstract
Pneumonia and its sequelae, acute lung injury, present unique challenges for pulmonary and critical care healthcare professionals, and these challenges have recently garnered global attention due to the ongoing Sars-CoV-2 pandemic. One limitation to translational investigation of acute lung injury, including its most severe manifestation (acute respiratory distress syndrome, ARDS) has been heterogeneity resulting from the clinical and physiologic diagnosis that represents a wide variety of etiologies. Recent efforts have improved our understanding and approach to heterogeneity by defining sub-phenotypes of ARDS although significant gaps in knowledge remain. Improving our mechanistic understanding of acute lung injury and its most common cause, infectious pneumonia, can advance our approach to precision targeted clinical interventions. Here, we review the pathogenesis of pneumonia and acute lung injury, including how respiratory infections and lung injury disrupt lung homoeostasis, and provide an overview of respiratory microbial pathogenesis, the lung microbiome, and interventions that have been demonstrated to improve outcomes-or not-in human clinical trials.
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18
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Amirgazin A, Shevtsov A, Karibayev T, Berdikulov M, Kozhakhmetova T, Syzdykova L, Ramankulov Y, Shustov AV. Highly pathogenic avian influenza virus of the A/H5N8 subtype, clade 2.3.4.4b, caused outbreaks in Kazakhstan in 2020. PeerJ 2022; 10:e13038. [PMID: 35256921 PMCID: PMC8898005 DOI: 10.7717/peerj.13038] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 02/09/2022] [Indexed: 01/11/2023] Open
Abstract
Background Large poultry die-offs happened in Kazakhstan during autumn of 2020. The birds' disease appeared to be avian influenza. Northern Kazakhstan was hit first and then the disease propagated across the country affecting eleven provinces. This study reports the results of full-genome sequencing of viruses collected during the outbreaks and investigation of their relationship to avian influenza virus isolates in the contemporary circulation in Eurasia. Methods Samples were collected from diseased birds during the 2020 outbreaks in Kazakhstan. Initial virus detection and subtyping was done using RT-PCR. Ten samples collected during expeditions to Northern and Southern Kazakhstan were used for full-genome sequencing of avian influenza viruses. Phylogenetic analysis was used to compare viruses from Kazakhstan to viral isolates from other world regions. Results Phylogenetic trees for hemagglutinin and neuraminidase show that viruses from Kazakhstan belong to the A/H5N8 subtype and to the hemagglutinin H5 clade 2.3.4.4b. Deduced hemagglutinin amino acid sequences in all Kazakhstan's viruses in this study contain the polybasic cleavage site (KRRKR-G) indicative of the highly pathogenic phenotype. Building phylogenetic trees with the Bayesian phylogenetics results in higher statistical support for clusters than using distance methods. The Kazakhstan's viruses cluster with isolates from Southern Russia, the Russian Caucasus, the Ural region, and southwestern Siberia. Other closely related prototypes are from Eastern Europe. The Central Asia Migratory Flyway passes over Kazakhstan and birds have intermediate stops in Northern Kazakhstan. It is postulated that the A/H5N8 subtype was introduced with migrating birds. Conclusion The findings confirm the introduction of the highly pathogenic avian influenza viruses of the A/Goose/Guangdong/96 (Gs/GD) H5 lineage in Kazakhstan. This virus poses a tangible threat to public health. Considering the results of this study, it looks justifiable to undertake measures in preparation, such as install sentinel surveillance for human cases of avian influenza in the largest pulmonary units, develop a human A/H5N8 vaccine and human diagnostics capable of HPAI discrimination.
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Affiliation(s)
- Asylulan Amirgazin
- National Center for Biotechnology, Nur-Sultan, Akmola Region, Kazakhstan
| | - Alexandr Shevtsov
- National Center for Biotechnology, Nur-Sultan, Akmola Region, Kazakhstan
| | - Talgat Karibayev
- National Reference Veterinary Center, Nur-Sultan, Akmola Region, Kazakhstan
| | - Maxat Berdikulov
- National Reference Veterinary Center, Nur-Sultan, Akmola Region, Kazakhstan
| | | | - Laura Syzdykova
- National Center for Biotechnology, Nur-Sultan, Akmola Region, Kazakhstan
| | - Yerlan Ramankulov
- National Center for Biotechnology, Nur-Sultan, Akmola Region, Kazakhstan,National Laboratory Astana, Nazarbayev University, Nur-Sultan, Akmola Region, Kazakhstan
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19
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Zhang M, Liu M, Bai S, Zhao C, Li Z, Xu J, Zhang X. Influenza A Virus-Host Specificity: An Ongoing Cross-Talk Between Viral and Host Factors. Front Microbiol 2021; 12:777885. [PMID: 34803997 PMCID: PMC8602901 DOI: 10.3389/fmicb.2021.777885] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 10/19/2021] [Indexed: 11/13/2022] Open
Abstract
One big threat from influenza A viruses (IAVs) is that novel viruses emerge from mutation alongside reassortment. Some of them have gained the capability to transmit into human from the avian reservoir. Understanding the molecular events and the involved factors in breaking the cross-species barrier holds important implication for the surveillance and prevention of potential influenza outbreaks. In this review, we summarize recent progresses, including several ground-breaking findings, in how the interaction between host and viral factors, exemplified by the PB2 subunit of the influenza virus RNA polymerase co-opting host ANP32 protein to facilitate transcription and replication of the viral genome, shapes the evolution of IAVs from host specificity to cross-species infection.
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Affiliation(s)
- Miaomiao Zhang
- Scientific Research Center, Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Veterinary Research Institute, Chinese Academic of Agricultural Sciences & Animal Influenza Virus Evolution and Pathogenesis Innovation Team of the Agricultural Science and Technology Innovation Team, Shanghai, China
| | - Mingbin Liu
- Scientific Research Center, Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai, China
| | - Shimeng Bai
- Scientific Research Center, Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai, China
| | - Chen Zhao
- Scientific Research Center, Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zejun Li
- Shanghai Veterinary Research Institute, Chinese Academic of Agricultural Sciences & Animal Influenza Virus Evolution and Pathogenesis Innovation Team of the Agricultural Science and Technology Innovation Team, Shanghai, China
| | - Jianqing Xu
- Scientific Research Center, Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xiaoyan Zhang
- Scientific Research Center, Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai, China
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20
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Marcuzzi A, Melloni E, Zauli G, Romani A, Secchiero P, Maximova N, Rimondi E. Autoinflammatory Diseases and Cytokine Storms-Imbalances of Innate and Adaptative Immunity. Int J Mol Sci 2021; 22:11241. [PMID: 34681901 PMCID: PMC8541037 DOI: 10.3390/ijms222011241] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 10/06/2021] [Accepted: 10/12/2021] [Indexed: 02/07/2023] Open
Abstract
Innate and adaptive immune responses have a well-known link and represent the distinctive origins of several diseases, many of which may be the consequence of the loss of balance between these two responses. Indeed, autoinflammation and autoimmunity represent the two extremes of a continuous spectrum of pathologic conditions with numerous overlaps in different pathologies. A common characteristic of these dysregulations is represented by hyperinflammation, which is an exaggerated response of the immune system, especially involving white blood cells, macrophages, and inflammasome activation with the hyperproduction of cytokines in response to various triggering stimuli. Moreover, hyperinflammation is of great interest, as it is one of the main manifestations of COVID-19 infection, and the cytokine storm and its most important components are the targets of the pharmacological treatments used to combat COVID-19 damage. In this context, the purpose of our review is to provide a focus on the pathogenesis of autoinflammation and, in particular, of hyperinflammation in order to generate insights for the identification of new therapeutic targets and strategies.
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Affiliation(s)
- Annalisa Marcuzzi
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (A.M.); (G.Z.); (A.R.)
| | - Elisabetta Melloni
- LTTA Centre, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (E.M.); (E.R.)
| | - Giorgio Zauli
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (A.M.); (G.Z.); (A.R.)
| | - Arianna Romani
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (A.M.); (G.Z.); (A.R.)
| | - Paola Secchiero
- LTTA Centre, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (E.M.); (E.R.)
| | - Natalia Maximova
- Bone Marrow Transplant Unit, Institute for Maternal and Child Health-IRCCS Burlo Garofolo, 34137 Trieste, Italy;
| | - Erika Rimondi
- LTTA Centre, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (E.M.); (E.R.)
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21
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Comparative Study of Bioactivity and Safety Evaluation of Ethanolic Extracts of Zanthoxylum schinifolium Fruit and Pericarp. Molecules 2021; 26:molecules26195919. [PMID: 34641463 PMCID: PMC8512002 DOI: 10.3390/molecules26195919] [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: 09/01/2021] [Revised: 09/21/2021] [Accepted: 09/27/2021] [Indexed: 01/14/2023] Open
Abstract
The fruit and pericarp of Zanthoxylum schinifolium (ZS) have been used in traditional medicine; however, few studies have characterized ZS fruit and pericarp. Therefore, in the present study, we evaluated the safety of ZS fruit (ZSF) and pericarp (ZSP) extracts and compared their bioactivity. To evaluate the safety of ZSF and ZSP, mutagenicity, cytotoxicity, and oxidative stress assays were performed and nontoxic concentration ranges were obtained. ZSP was found to be superior to ZSF in terms of its antimutagenic, antioxidant, and anti-inflammatory activities. In the S9 mix, the mutation inhibition rate of ZSP was close to 100% at concentrations exceeding 625 µg·plate−1 for both the TA98 and TA100 strains. ZSP exhibited efficient DPPH (IC50 = 75.6 ± 6.1 µg·mL−1) and ABTS (IC50 = 57.4 ± 6 µg·mL−1) scavenging activities. ZSP inhibited the release of cytokines, involved in IL-1β (IC50 = 134.4 ± 7.8), IL-6 (IC50 = 262.8 ± 11.2), and TNF-α (IC50 = 223.8 ± 5.8). These results indicate that ZSP contains a higher amount of biochemicals than ZSF, or that ZSP contains unique biochemicals. In conclusion, for certain physiological activities, the use of ZSP alone may be more beneficial than the combined use of ZSF and ZSP.
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Wan X, Li J, Wang Y, Yu X, He X, Shi J, Deng G, Zeng X, Tian G, Li Y, Jiang Y, Guan Y, Li C, Shao F, Chen H. H7N9 virus infection triggers lethal cytokine storm by activating gasdermin E-mediated pyroptosis of lung alveolar epithelial cells. Natl Sci Rev 2021; 9:nwab137. [PMID: 35087672 PMCID: PMC8788236 DOI: 10.1093/nsr/nwab137] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 07/13/2021] [Accepted: 07/22/2021] [Indexed: 01/03/2023] Open
Abstract
The H7N9 influenza virus emerged in China in 2013, causing more than 1560 human infections, 39% of which were fatal. A ‘cytokine storm’ in the lungs of H7N9 patients has been linked to a poor prognosis and death; however, the underlying mechanism that triggers the cytokine storm is unknown. Here, we found that efficient replication of the H7N9 virus in mouse lungs activates gasdermin E (GSDME)-mediated pyroptosis in alveolar epithelial cells, and that the released cytosolic contents then trigger a cytokine storm. Knockout of Gsdme switched the manner of death of A549 and human primary alveolar epithelial cells from pyroptosis to apoptosis upon H7N9 virus infection, and Gsdme knockout mice survived H7N9 virus lethal infection. Our findings reveal that GSDME activation is a key and unique mechanism for the pulmonary cytokine storm and lethal outcome of H7N9 virus infection and thus opens a new door for the development of antivirals against the H7N9 virus.
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Affiliation(s)
- Xiaopeng Wan
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China
| | - Jiqing Li
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China
| | - Yupeng Wang
- National Institute of Biological Sciences, Beijing 102206, China
| | - Xiaofei Yu
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China
| | - Xijun He
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China
| | - Jianzhong Shi
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China
| | - Guohua Deng
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China
| | - Xianying Zeng
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China
| | - Guobin Tian
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China
| | - Yanbing Li
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China
| | - Yongping Jiang
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China
| | - Yuntao Guan
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China
| | - Chengjun Li
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China
| | - Feng Shao
- National Institute of Biological Sciences, Beijing 102206, China
| | - Hualan Chen
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China
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Abstract
Influenza infection poses significant risk for solid organ transplant recipients who often experience more severe infection with increased rates of complications, including those relating to the allograft. Although symptoms of influenza experienced by transplant recipients are similar to that of the general population, fever is not a ubiquitous symptom and lymphopenia is common. Annual inactivated influenza vaccine is recommended for all transplant recipients. Newer strategies such as using a higher dose vaccine or multiple doses in the same season appear to provide greater immunogenicity. Neuraminidase inhibitors are the mainstay of treatment and chemoprophylaxis although resistance may occur in the transplant setting. Influenza therapeutics are advancing, including the recent licensure of baloxavir; however, many remain to be evaluated in transplant recipients and are not yet in routine clinical use. Further population-based studies spanning multiple influenza seasons are needed to enhance our understanding of influenza epidemiology in solid organ transplant recipients. Specific assessment of newer influenza therapeutics in transplant recipients and refinement of prevention strategies are vital to reducing morbidity and mortality.
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Affiliation(s)
- Tina M Marinelli
- Division of Infectious Diseases, Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
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Dueck NP, Epstein S, Franquet T, Moore CC, Bueno J. Atypical Pneumonia: Definition, Causes, and Imaging Features. Radiographics 2021; 41:720-741. [PMID: 33835878 DOI: 10.1148/rg.2021200131] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Pneumonia is among the most common causes of death worldwide. The epidemiologic and clinical heterogeneity of pneumonia results in challenges in diagnosis and treatment. There is inconsistency in the definition of the group of microorganisms that cause "atypical pneumonia." Nevertheless, the use of this term in the medical and radiologic literature is common. Among the causes of community-acquired pneumonia, atypical bacteria are responsible for approximately 15% of cases. Zoonotic and nonzoonotic bacteria, as well as viruses, have been considered among the causes of atypical pneumonia in a patient who is immunocompetent and have been associated with major community outbreaks of respiratory infection, with relevant implications in public health policies. Considering the difficulty of isolating atypical microorganisms and the significant overlap in clinical manifestations, a targeted empirical therapy is not possible. Imaging plays an important role in the diagnosis and management of atypical pneumonia, as in many cases its findings may first suggest the possibility of an atypical infection. Clarifying and unifying the definition of atypical pneumonia among the medical community, including radiologists, are of extreme importance. The prompt diagnosis and prevention of community spread of some atypical microorganisms can have a relevant impact on local, regional, and global health policies. ©RSNA, 2021.
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Affiliation(s)
- Nicholas P Dueck
- From the Department of Radiology and Medical Imaging (N.P.D., S.E., J.B.) and Department of Infectious Diseases and International Health (C.C.M.), University of Virginia Medical Center, 1215 Lee St, PO Box 800170, Charlottesville, VA 22908; and Department of Radiology, Hospital de Sant Pau-Universidad Autónoma de Barcelona, Barcelona, Spain (T.F.)
| | - Samantha Epstein
- From the Department of Radiology and Medical Imaging (N.P.D., S.E., J.B.) and Department of Infectious Diseases and International Health (C.C.M.), University of Virginia Medical Center, 1215 Lee St, PO Box 800170, Charlottesville, VA 22908; and Department of Radiology, Hospital de Sant Pau-Universidad Autónoma de Barcelona, Barcelona, Spain (T.F.)
| | - Tomás Franquet
- From the Department of Radiology and Medical Imaging (N.P.D., S.E., J.B.) and Department of Infectious Diseases and International Health (C.C.M.), University of Virginia Medical Center, 1215 Lee St, PO Box 800170, Charlottesville, VA 22908; and Department of Radiology, Hospital de Sant Pau-Universidad Autónoma de Barcelona, Barcelona, Spain (T.F.)
| | - Christopher C Moore
- From the Department of Radiology and Medical Imaging (N.P.D., S.E., J.B.) and Department of Infectious Diseases and International Health (C.C.M.), University of Virginia Medical Center, 1215 Lee St, PO Box 800170, Charlottesville, VA 22908; and Department of Radiology, Hospital de Sant Pau-Universidad Autónoma de Barcelona, Barcelona, Spain (T.F.)
| | - Juliana Bueno
- From the Department of Radiology and Medical Imaging (N.P.D., S.E., J.B.) and Department of Infectious Diseases and International Health (C.C.M.), University of Virginia Medical Center, 1215 Lee St, PO Box 800170, Charlottesville, VA 22908; and Department of Radiology, Hospital de Sant Pau-Universidad Autónoma de Barcelona, Barcelona, Spain (T.F.)
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25
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Noisumdaeng P, Roytrakul T, Prasertsopon J, Pooruk P, Lerdsamran H, Assanasen S, Kitphati R, Auewarakul P, Puthavathana P. T cell mediated immunity against influenza H5N1 nucleoprotein, matrix and hemagglutinin derived epitopes in H5N1 survivors and non-H5N1 subjects. PeerJ 2021; 9:e11021. [PMID: 33854839 PMCID: PMC7955671 DOI: 10.7717/peerj.11021] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Accepted: 02/06/2021] [Indexed: 12/12/2022] Open
Abstract
Background Protection against the influenza virus by a specific antibody is relatively strain specific; meanwhile broader immunity may be conferred by cell-mediated immune response to the conserved epitopes across influenza virus subtypes. A universal broad-spectrum influenza vaccine which confronts not only seasonal influenza virus, but also avian influenza H5N1 virus is promising. Methods This study determined the specific and cross-reactive T cell responses against the highly pathogenic avian influenza A (H5N1) virus in four survivors and 33 non-H5N1 subjects including 10 H3N2 patients and 23 healthy individuals. Ex vivo IFN-γ ELISpot assay using overlapping peptides spanning the entire nucleoprotein (NP), matrix (M) and hemagglutinin (HA) derived from A/Thailand/1(KAN-1)/2004 (H5N1) virus was employed in adjunct with flow cytometry for determining T cell functions. Microneutralization (microNT) assay was performed to determine the status of previous H5N1 virus infection. Results IFN-γ ELISpot assay demonstrated that survivors nos. 1 and 2 had markedly higher T cell responses against H5N1 NP, M and HA epitopes than survivors nos. 3 and 4; and the magnitude of T cell responses against NP were higher than that of M and HA. Durability of the immunoreactivity persisted for as long as four years after disease onset. Upon stimulation by NP in IFN-γ ELISpot assay, 60% of H3N2 patients and 39% of healthy subjects exhibited a cross-reactive T cell response. The higher frequency and magnitude of responses in H3N2 patients may be due to blood collection at the convalescent phase of the patients. In H5N1 survivors, the effector peptide-specific T cells generated from bulk culture PBMCs by in vitro stimulation displayed a polyfunction by simultaneously producing IFN-γ and TNF-α, together with upregulation of CD107a in recognition of the target cells pulsed with peptide or infected with rVac-NP virus as investigated by flow cytometry. Conclusions This study provides an insight into the better understanding on the homosubtypic and heterosubtypic T cell-mediated immune responses in H5N1 survivors and non-H5N1 subjects. NP is an immunodominant target of cross-recognition owing to its high conservancy. Therefore, the development of vaccine targeting the conserved NP may be a novel strategy for influenza vaccine design.
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Affiliation(s)
- Pirom Noisumdaeng
- Faculty of Public Health, Thammasat University, Khlong Luang, Pathum Thani, Thailand.,Thammasat University Research Unit in Modern Microbiology and Public Health Genomics, Thammasat University, Khlong Luang, Pathum Thani, Thailand.,Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok-noi, Bangkok, Thailand
| | - Thaneeya Roytrakul
- National Center for Genetic Engineering and Biotechnology, Khlong Luang, Pathum Thani, Thailand
| | - Jarunee Prasertsopon
- Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand
| | - Phisanu Pooruk
- The Government Pharmaceutical Organization, Biological Product Vaccine Production Plant, Kaengkhoi, Saraburi, Thailand
| | - Hatairat Lerdsamran
- Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand
| | - Susan Assanasen
- Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok-noi, Bangkok, Thailand
| | | | - Prasert Auewarakul
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok-noi, Bangkok, Thailand
| | - Pilaipan Puthavathana
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok-noi, Bangkok, Thailand.,Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand
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26
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Kircheis R, Haasbach E, Lueftenegger D, Heyken WT, Ocker M, Planz O. NF-κB Pathway as a Potential Target for Treatment of Critical Stage COVID-19 Patients. Front Immunol 2020; 11:598444. [PMID: 33362782 PMCID: PMC7759159 DOI: 10.3389/fimmu.2020.598444] [Citation(s) in RCA: 148] [Impact Index Per Article: 29.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 11/27/2020] [Indexed: 12/15/2022] Open
Abstract
Patients infected with SARS-CoV-2 show a wide spectrum of clinical manifestations ranging from mild febrile illness and cough up to acute respiratory distress syndrome, multiple organ failure, and death. Data from patients with severe clinical manifestations compared to patients with mild symptoms indicate that highly dysregulated exuberant inflammatory responses correlate with severity of disease and lethality. Epithelial-immune cell interactions and elevated cytokine and chemokine levels, i.e. cytokine storm, seem to play a central role in severity and lethality in COVID-19. The present perspective places a central cellular pro-inflammatory signal pathway, NF-κB, in the context of recently published data for COVID-19 and provides a hypothesis for a therapeutic approach aiming at the simultaneous inhibition of whole cascades of pro-inflammatory cytokines and chemokines. The simultaneous inhibition of multiple cytokines/chemokines is expected to have much higher therapeutic potential as compared to single target approaches to prevent cascade (i.e. redundant, triggering, amplifying, and synergistic) effects of multiple induced cytokines and chemokines in critical stage COVID-19 patients.
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Affiliation(s)
| | - Emanuel Haasbach
- Institute of Cell Biology and Immunology, Eberhard Karls University Tuebingen, Tuebingen, Germany
| | | | | | - Matthias Ocker
- Institute for Surgical Research, Philipps University of Marburg, Marburg, Germany
| | - Oliver Planz
- Institute of Cell Biology and Immunology, Eberhard Karls University Tuebingen, Tuebingen, Germany
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27
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Rafiullah M, Siddiqui K. Corticosteroid use in viral pneumonia: experience so far and the dexamethasone breakthrough in coronavirus disease-2019. J Comp Eff Res 2020; 9:1247-1254. [PMID: 33245242 PMCID: PMC7694443 DOI: 10.2217/cer-2020-0146] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Dexamethasone was shown to decrease the mortality in coronavirus disease-2019 (COVID-19) recently. Use of corticosteroids was harmful in other coronavirus infections previously. WHO recommended against routine use of corticosteroids in COVID-19. In view of these, we reviewed the evidence about the use of corticosteroids in virus-induced acute respiratory distress syndrome (ARDS). Corticosteroids are beneficial in ARDS regardless of etiology. However, they increased the mortality rate in influenza-associated ARDS. In SARS and the Middle East respiratory syndrome, corticosteroids increased the mortality, delayed the viral clearance and increased the length of hospital stay. In the case of COVID-19, the available evidence from retrospective and observational studies is inconclusive about the corticosteroid use. Low-dose therapies appear to be effective. Evidence from a randomized control study found dexamethasone is effective in decreasing mortality in severe COVID-19 cases. More studies are needed to validate the benefit of corticosteroids in COVID-19.
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Affiliation(s)
- Mohamed Rafiullah
- Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Khalid Siddiqui
- Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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28
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Eccles R. Why is temperature sensitivity important for the success of common respiratory viruses? Rev Med Virol 2020; 31:1-8. [PMID: 32776651 PMCID: PMC7435572 DOI: 10.1002/rmv.2153] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 07/22/2020] [Accepted: 07/22/2020] [Indexed: 01/01/2023]
Abstract
This review explores the idea that temperature sensitivity is an important factor in determining the success of respiratory viruses as human parasites. The review discusses several questions. What is viral temperature sensitivity? At what range of temperatures are common respiratory viruses sensitive? What is the mechanism for their temperature sensitivity? What is the range of temperature along the human airway? What is it that makes respiratory viruses such successful parasites of the human airway? What is the role of temperature sensitivity in respiratory zoonoses? A definition of temperature sensitivity is proposed, as “the property of a virus to replicate poorly or not at all, at the normal body temperature of the host (restrictive temperature), but to replicate well at the lower temperatures found in the upper airway of the host (permissive temperature).” Temperature sensitivity may influence the success of a respiratory virus in several ways. Firstly; by restricting the infection to the upper airways and reducing the chance of systemic infection that may reduce host mobility and increase mortality, and thus limit the spread of the virus. Secondly; by causing a mild upper airway illness with a limited immune response compared to systemic infection, which means that persistent herd immunity does not develop to the same extent as with systemic infections, and re‐infection may occur later. Thirdly; infection of the upper airway triggers local reflex rhinorrhea, coughing and sneezing which aid the exit of the virus from the host and the spread of infection in the community.
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Affiliation(s)
- Ronald Eccles
- Emeritus Professor, Cardiff School of Biosciences, Cardiff University, UK
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29
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Controlling Avian Influenza Virus in Bangladesh: Challenges and Recommendations. Viruses 2020; 12:v12070751. [PMID: 32664683 PMCID: PMC7412482 DOI: 10.3390/v12070751] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 07/08/2020] [Accepted: 07/08/2020] [Indexed: 01/01/2023] Open
Abstract
Avian influenza virus (AIV) remains a huge challenge for poultry production with negative repercussions for micro- and macro-economy and public health in Bangladesh. High (HP) H5N1 and low pathogenicity (LP) H9N2 AIV are currently endemic in poultry, and both have been reported to infect humans sporadically. Multiple virus introductions of different clades of HPAIV H5N1, reassorted genotypes, and on-going diversification of LPAIV H9N2 create a highly volatile virological environment which potentially implicates increased virulence, adaptation to new host species, and subsequent zoonotic transmission. Allotropy of poultry rearing systems and supply chains further increase the risk of virus spreading, which leads to human exposure and fosters the emergence of new potentially pre-pandemic virus strains. Here, we review the epidemiology, focusing on (i) risk factors for virus spreading, (ii) viral genetic evolution, and (iii) options for AIV control in Bangladesh. It is concluded that improved control strategies would profit from the integration of various intervention tools, including effective vaccination, enhanced biosecurity practice, and improved awareness of producers and traders, although widespread household poultry rearing significantly interferes with any such strategies. Nevertheless, continuous surveillance associated with rapid diagnosis and thorough virus characterization is the basis of such strategies.
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30
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Yang H, Carney PJ, Chang JC, Stevens J. Molecular characterization and three-dimensional structures of avian H8, H11, H14, H15 and swine H4 influenza virus hemagglutinins. Heliyon 2020; 6:e04068. [PMID: 32529072 PMCID: PMC7281811 DOI: 10.1016/j.heliyon.2020.e04068] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 03/25/2020] [Accepted: 05/21/2020] [Indexed: 11/08/2022] Open
Abstract
Of the eighteen hemagglutinin (HA) subtypes (H1–H18) that have been identified in bats and aquatic birds, many HA subtypes have been structurally characterized. However, several subtypes (H8, H11 and H12) still require characterization. To better understand all of these HA subtypes at the molecular level, HA structures from an A(H4N6) (A/swine/Missouri/A01727926/2015), an A(H8N4) (A/turkey/Ontario/6118/1968), an A(H11N9) (A/duck/Memphis/546/1974), an A(H14N5) A/mallard/Gurjev/263/1982, and an A(H15N9) (A/wedge-tailed shearwater/Western Australia/2576/1979 were determined by X-ray crystallography at 2.2Å, 2.3Å, 2.8Å, 3.0Å and 2.5Å resolution, respectively. The interactions between these viruses and host receptors were studied utilizing glycan-binding analyses with their recombinant HA. The data show that all avian HAs retain their strict binding preference to avian receptors, whereas swine H4 has a weak human receptor binding. The molecular characterization and structural analyses of the HA from these zoonotic influenza viruses not only provide a deeper appreciation and understanding of the structure of all HA subtypes, but also re-iterate why continuous global surveillance is needed.
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Affiliation(s)
- Hua Yang
- Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA
| | - Paul J Carney
- Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA
| | - Jessie C Chang
- Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA
| | - James Stevens
- Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA
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Amouzougan EA, Lira R, Klimecki WT. Chronic exposure to arsenite enhances influenza virus infection in cultured cells. J Appl Toxicol 2020; 40:458-469. [PMID: 31960482 PMCID: PMC7931812 DOI: 10.1002/jat.3918] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 09/30/2019] [Accepted: 10/02/2019] [Indexed: 12/13/2022]
Abstract
Arsenic is a ubiquitous environmental toxicant that has been associated with human respiratory diseases. In humans, arsenic exposure has been associated with increased risk of respiratory infection. Considering the existing epidemiological evidence and the well-established impact of arsenic on epithelial cell biology, we posited that the effect of arsenic exposure in epithelial cells could enhance viral infection. In this study, we characterized influenza virus A/WSN/33 (H1N1) infection in Madin-Darby Canine Kidney (MDCK) cells chronically exposed to low levels of sodium arsenite (75 ppb). We observed a 27.3-fold increase in viral matrix (M2) protein (24 hours postinfection [p.i.]), a 1.35-fold increase in viral mRNA levels, and a 126% increase in plaque area in arsenite-exposed MDCK cells (48 hours p.i.). Arsenite exposure resulted in 114% increase in virus attachment-positive cells (2 hours p.i.) and 224% increase in α-2,3 sialic acid-positive cells. Interestingly, chronic exposure to arsenite reduced the effect of the antiviral drug, oseltamivir in MDCK cells. We also found that exposure to sodium arsenite resulted in a 4.4-fold increase in viral mRNA levels and significantly increased cytotoxicity in influenza A/Udorn/72 (H3N2) infected BEAS-2B cells. This study suggests that chronic arsenite exposure could result in enhanced influenza infection in epithelial cells, and that this may be mediated through increased sialic acid binding. Finally, the decreased effectiveness of the anti-influenza drug, oseltamivir, in arsenite-exposed cells raises substantial public health concerns if this effect translates to arsenic-exposed, influenza-infected people.
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Affiliation(s)
- Eva A. Amouzougan
- Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, Arizona 85724, United States
| | - Ricardo Lira
- Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, Arizona 85724, United States
| | - Walter T. Klimecki
- Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, Arizona 85724, United States
- College of Veterinary Medicine, The University of Arizona, Tucson, Arizona 85724, United States
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32
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The Role of Innate Leukocytes during Influenza Virus Infection. J Immunol Res 2019; 2019:8028725. [PMID: 31612153 PMCID: PMC6757286 DOI: 10.1155/2019/8028725] [Citation(s) in RCA: 66] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Accepted: 07/15/2019] [Indexed: 02/07/2023] Open
Abstract
Influenza virus infection is a serious threat to humans and animals, with the potential to cause severe pneumonia and death. Annual vaccination strategies are a mainstay to prevent complications related to influenza. However, protection from the emerging subtypes of influenza A viruses (IAV) even in vaccinated individuals is challenging. Innate immune cells are the first cells to respond to IAV infection in the respiratory tract. Virus replication-induced production of cytokines from airway epithelium recruits innate immune cells to the site of infection. These leukocytes, namely, neutrophils, monocytes, macrophages, dendritic cells, eosinophils, natural killer cells, innate lymphoid cells, and γδ T cells, become activated in response to IAV, to contain the virus and protect the airway epithelium while triggering the adaptive arm of the immune system. This review addresses different anti-influenza virus schemes of innate immune cells and how these cells fine-tune the balance between immunoprotection and immunopathology during IAV infection. Detailed understanding on how these innate responders execute anti-influenza activity will help to identify novel therapeutic targets to halt IAV replication and associated immunopathology.
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33
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Ong HK, Yong CY, Tan WS, Yeap SK, Omar AR, Razak MA, Ho KL. An Influenza A Vaccine Based on the Extracellular Domain of Matrix 2 Protein Protects BALB/C Mice Against H1N1 and H3N2. Vaccines (Basel) 2019; 7:vaccines7030091. [PMID: 31430965 PMCID: PMC6789677 DOI: 10.3390/vaccines7030091] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 08/14/2019] [Accepted: 08/14/2019] [Indexed: 01/27/2023] Open
Abstract
Current seasonal influenza A virus (IAV) vaccines are strain-specific and require annual reconstitution to accommodate the viral mutations. Mismatches between the vaccines and circulating strains often lead to high morbidity. Hence, development of a universal influenza A vaccine targeting all IAV strains is urgently needed. In the present study, the protective efficacy and immune responses induced by the extracellular domain of Matrix 2 protein (M2e) displayed on the virus-like particles of Macrobrachium rosenbergii nodavirus (NvC-M2ex3) were investigated in BALB/c mice. NvC-M2ex3 was demonstrated to be highly immunogenic even in the absence of adjuvants. Higher anti-M2e antibody titers corresponded well with increased survival, reduced immunopathology, and morbidity of the infected BALB/c mice. The mice immunized with NvC-M2ex3 exhibited lower H1N1 and H3N2 virus replication in the respiratory tract and the vaccine activated the production of different antiviral cytokines when they were challenged with H1N1 and H3N2. Collectively, these results suggest that NvC-M2ex3 could be a potential universal influenza A vaccine.
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Affiliation(s)
- Hui Kian Ong
- Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Malaysia
| | - Chean Yeah Yong
- Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Malaysia
- Institute of Bioscience, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Malaysia
| | - Wen Siang Tan
- Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Malaysia
- Institute of Bioscience, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Malaysia
| | - Swee Keong Yeap
- Department of Marine Biotechnology, China-ASEAN College of Marine Sciences, Xiamen University Malaysia, Jalan Sunsuria, Bandar Sunsuria, Sepang 43900, Selangor, Malaysia
| | - Abdul Rahman Omar
- Institute of Bioscience, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Malaysia
- Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Malaysia
| | - Mariatulqabtiah Abdul Razak
- Institute of Bioscience, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Malaysia
- Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Malaysia
| | - Kok Lian Ho
- Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Malaysia.
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Elbahesh H, Saletti G, Gerlach T, Rimmelzwaan GF. Broadly protective influenza vaccines: design and production platforms. Curr Opin Virol 2019; 34:1-9. [DOI: 10.1016/j.coviro.2018.11.005] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Accepted: 11/07/2018] [Indexed: 01/04/2023]
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Shi J, Deng G, Ma S, Zeng X, Yin X, Li M, Zhang B, Cui P, Chen Y, Yang H, Wan X, Liu L, Chen P, Jiang Y, Guan Y, Liu J, Gu W, Han S, Song Y, Liang L, Qu Z, Hou Y, Wang X, Bao H, Tian G, Li Y, Jiang L, Li C, Chen H. Rapid Evolution of H7N9 Highly Pathogenic Viruses that Emerged in China in 2017. Cell Host Microbe 2018; 24:558-568.e7. [PMID: 30269969 DOI: 10.1016/j.chom.2018.08.006] [Citation(s) in RCA: 195] [Impact Index Per Article: 27.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Revised: 06/29/2018] [Accepted: 08/13/2018] [Indexed: 01/21/2023]
Abstract
H7N9 low pathogenic influenza viruses emerged in China in 2013 and mutated to highly pathogenic strains in 2017, resulting in human infections and disease in chickens. To control spread, a bivalent H5/H7 inactivated vaccine was introduced in poultry in September 2017. To monitor virus evolution and vaccine efficacy, we collected 53,884 poultry samples across China from February 2017 to January 2018. We isolated 252 H7N9 low pathogenic viruses, 69 H7N9 highly pathogenic viruses, and one H7N2 highly pathogenic virus, of which two low pathogenic and 14 highly pathogenic strains were collected after vaccine introduction. Genetic analysis of highly pathogenic strains revealed nine genotypes, one of which is predominant and widespread and contains strains exhibiting high virulence in mice. Additionally, some H7N9 and H7N2 viruses carrying duck virus genes are lethal in ducks. Thus, although vaccination reduced H7N9 infections, the increased virulence and expanded host range to ducks pose new challenges.
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Affiliation(s)
- Jianzhong Shi
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Guohua Deng
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Shujie Ma
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Xianying Zeng
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Xin Yin
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Mei Li
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Bo Zhang
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Pengfei Cui
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Yan Chen
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Huanliang Yang
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Xiaopeng Wan
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Liling Liu
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Pucheng Chen
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Yongping Jiang
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Yuntao Guan
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Jinxiong Liu
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Wenli Gu
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Shuyu Han
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Yangming Song
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Libin Liang
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Zhiyuan Qu
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Yujie Hou
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Xiurong Wang
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Hongmei Bao
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Guobin Tian
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Yanbing Li
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Li Jiang
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Chengjun Li
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China
| | - Hualan Chen
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang 150069, People's Republic of China.
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Mostafa A, Abdelwhab EM, Mettenleiter TC, Pleschka S. Zoonotic Potential of Influenza A Viruses: A Comprehensive Overview. Viruses 2018; 10:v10090497. [PMID: 30217093 PMCID: PMC6165440 DOI: 10.3390/v10090497] [Citation(s) in RCA: 178] [Impact Index Per Article: 25.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Revised: 08/24/2018] [Accepted: 09/13/2018] [Indexed: 02/06/2023] Open
Abstract
Influenza A viruses (IAVs) possess a great zoonotic potential as they are able to infect different avian and mammalian animal hosts, from which they can be transmitted to humans. This is based on the ability of IAV to gradually change their genome by mutation or even reassemble their genome segments during co-infection of the host cell with different IAV strains, resulting in a high genetic diversity. Variants of circulating or newly emerging IAVs continue to trigger global health threats annually for both humans and animals. Here, we provide an introduction on IAVs, highlighting the mechanisms of viral evolution, the host spectrum, and the animal/human interface. Pathogenicity determinants of IAVs in mammals, with special emphasis on newly emerging IAVs with pandemic potential, are discussed. Finally, an overview is provided on various approaches for the prevention of human IAV infections.
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Affiliation(s)
- Ahmed Mostafa
- Institute of Medical Virology, Justus Liebig University Giessen, Schubertstrasse 81, 35392 Giessen, Germany.
- Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Giza 12622, Egypt.
| | - Elsayed M Abdelwhab
- Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493 Greifswald-Insel Riems, Germany.
| | - Thomas C Mettenleiter
- Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493 Greifswald-Insel Riems, Germany.
| | - Stephan Pleschka
- Institute of Medical Virology, Justus Liebig University Giessen, Schubertstrasse 81, 35392 Giessen, Germany.
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Heaton BE, Kennedy EM, Dumm RE, Harding AT, Sacco MT, Sachs D, Heaton NS. A CRISPR Activation Screen Identifies a Pan-avian Influenza Virus Inhibitory Host Factor. Cell Rep 2018; 20:1503-1512. [PMID: 28813663 DOI: 10.1016/j.celrep.2017.07.060] [Citation(s) in RCA: 109] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Revised: 07/17/2017] [Accepted: 07/21/2017] [Indexed: 02/02/2023] Open
Abstract
Influenza A virus (IAV) is a pathogen that poses significant risks to human health. It is therefore critical to develop strategies to prevent influenza disease. Many loss-of-function screens have been performed to identify the host proteins required for viral infection. However, there has been no systematic screen to identify the host factors that, when overexpressed, are sufficient to prevent infection. In this study, we used CRISPR/dCas9 activation technology to perform a genome-wide overexpression screen to identify IAV restriction factors. The major hit from our screen, B4GALNT2, showed inhibitory activity against influenza viruses with an α2,3-linked sialic acid receptor preference. B4GALNT2 overexpression prevented the infection of every avian influenza virus strain tested, including the H5, H9, and H7 subtypes, which have previously caused disease in humans. Thus, we have used CRISPR/dCas9 activation technology to identify a factor that can abolish infection by avian influenza viruses.
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Affiliation(s)
- Brook E Heaton
- Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA
| | - Edward M Kennedy
- Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA
| | - Rebekah E Dumm
- Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA
| | - Alfred T Harding
- Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA
| | - Matthew T Sacco
- Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA
| | - David Sachs
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Nicholas S Heaton
- Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.
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Population Study about the Attitude toward Organ Xenotransplantation in the Population from Eastern Europe Resident in Southeast Spain. Int J Artif Organs 2018. [DOI: 10.1177/039139881003300105] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background The objective of this paper is to analyze the attitude toward xenotransplantation and to determine the variables that influence this attitude in the population of southeast Spain who were born in Eastern European countries. Methods A random sample was taken of natives from Eastern Europe residing in southeast Spain (n=320). The sample was obtained randomly between November 2005 and April 2006 and stratified according to the respondents' nationality. Attitude was evaluated using a validated questionnaire which was self-administered and completed anonymously. The control group was a random sample of the native Spanish population (n=250). The statistical analysis used included Student's t-test, the chi-square test, Fisher's exact test, and a logistic regression analysis. Results The questionnaire completion rate was 83% (n=267). Regarding the use of animal organs for transplantation in humans, if the outcome were similar to that achieved when using human organs, 43% (n=114) would be in favor, 32% (n=86) undecided, and the remaining 25% (n=67) would be against it. This attitude is less favorable than in the control group (43% versus 74%, p<0.001). The attitude was related to the following factors: 1) the country of origin (p<0.001); 2) participation in social help activities (p<0.001); 3) discussion on organ donation and transplantation within the family (p=0.005); 4) previous experience of organ donation and transplantation (p=0.002); 5) the respondent's religion (p=0.002); 6) knowing that one's partner had a favorable attitude toward transplantation (p<0.001); 7) the respondent's belief that he or she might need a transplant in the future (p<0.001); 8) the attitude toward human donation, both from cadaver (p<0.001) and living (p<0.001) donors. The following were also independent variables in the subsequent multivariate analysis: 1) favorable attitude toward cadaver organ donation (OR=4.998); 2) previous experience of donation (OR=2.857); 3) partner's attitude against transplantation (OR=0.079); and 4) attitude toward living donation (OR=12.703). Conclusions The attitude toward xenotransplantation is less positive among Eastern Europeans living in Spain than in the native Spanish population and is influenced by many psychosocial factors that are mainly related to human organ donation.
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Baowan D, Hill JM, Bacsa W. Continuous approximation for interaction energy of adamantane encapsulated inside carbon nanotubes. Chem Phys Lett 2018. [DOI: 10.1016/j.cplett.2017.12.064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Kim MC, Lee YN, Kim YJ, Choi HJ, Kim KH, Lee YJ, Kang SM. Immunogenicity and efficacy of replication-competent recombinant influenza virus carrying multimeric M2 extracellular domains in a chimeric hemagglutinin conjugate. Antiviral Res 2017; 148:43-52. [PMID: 29107058 DOI: 10.1016/j.antiviral.2017.10.018] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Revised: 10/17/2017] [Accepted: 10/23/2017] [Indexed: 01/12/2023]
Abstract
Current influenza vaccines provide hemagglutinin (HA) strain-specific protection. To improve cross protection, we engineered replication-competent influenza A virus to express tandem repeats of heterologous M2 extracellular (M2e) domains in a chimeric HA. M2e epitopes conjugated to HA glycoproteins (M2e4x-HA) were found to be expressed on the surfaces of a replicable influenza virus as examined by electron microscopy. The recombinant influenza virus containing M2e4x-HA was moderately attenuated but superior to the parental virus in inducing M2e specific antibodies without compromising HA immunogenicity. Recombinant influenza virus immune mice showed better cross protection than parental virus immune mice. Immune sera from the mice with inoculation of live recombinant influenza virus expressing M2e4x-HA were effective in conferring protection against H1, H3, and H5 subtype influenza viruses. This study indicates that recombinant influenza virus expressing conserved protective epitopes in an HA chimeric form can provide a new approach for improving the efficacy of influenza vaccines.
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Affiliation(s)
- Min-Chul Kim
- Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, 30303, USA; Animal and Plant Quarantine Agency, Gimcheon, Gyeongsangbukdo, 39660, Republic of Korea
| | - Yu-Na Lee
- Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, 30303, USA; Animal and Plant Quarantine Agency, Gimcheon, Gyeongsangbukdo, 39660, Republic of Korea
| | - Yu-Jin Kim
- Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, 30303, USA
| | - Hyo-Jick Choi
- Department of Chemical and Materials Engineering, University of Alberta, AB, T6G 2V4, Canada
| | - Ki-Hye Kim
- Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, 30303, USA
| | - Youn-Jeong Lee
- Animal and Plant Quarantine Agency, Gimcheon, Gyeongsangbukdo, 39660, Republic of Korea
| | - Sang-Moo Kang
- Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, 30303, USA.
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Ji Y, White YJ, Hadden JA, Grant OC, Woods RJ. New insights into influenza A specificity: an evolution of paradigms. Curr Opin Struct Biol 2017; 44:219-231. [PMID: 28675835 DOI: 10.1016/j.sbi.2017.06.001] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Revised: 05/29/2017] [Accepted: 06/02/2017] [Indexed: 02/05/2023]
Abstract
Understanding the molecular origin of influenza receptor specificity is complicated by the paucity of quantitative affinity measurements, and the qualitative and variable nature of glycan array data. Further obstacles arise from the varied impact of viral glycosylation and the relatively narrow spectrum of biologically relevant receptors present on glycan arrays. A survey of receptor conformational properties is presented, leading to the conclusion that conformational entropy plays a key role in defining specificity, as does the newly reported ability of biantennary receptors that terminate in Siaα2-6Gal sequences to form bidentate interactions to two binding sites in a hemagglutinin trimer. Bidentate binding provides a functional explanation for the observation that Siaα2-6 receptors adopt an open-umbrella topology when bound to hemagglutinins from human-infective viruses, and calls for a reassessment of virus avidity and tissue tropism.
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Affiliation(s)
- Ye Ji
- Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Rd, Athens, GA 30602, United States
| | - Yohanna Jb White
- Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Rd, Athens, GA 30602, United States
| | - Jodi A Hadden
- Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Rd, Athens, GA 30602, United States
| | - Oliver C Grant
- Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Rd, Athens, GA 30602, United States
| | - Robert J Woods
- Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Rd, Athens, GA 30602, United States.
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Mosaad Z, Arafa A, Hussein HA, Shalaby MA. Mutation signature in neuraminidase gene of avian influenza H9N2/G1 in Egypt. Virusdisease 2017; 28:164-173. [PMID: 28770242 DOI: 10.1007/s13337-017-0367-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2016] [Accepted: 02/18/2017] [Indexed: 10/19/2022] Open
Abstract
The low pathogenic avian influenza (LPAI) H9N2 subtype has become the most prevalent and widespread in many Asian and Middle Eastern countries. It causes an enzootic situation in commercial poultry and known as a potential facilitator virus that can be transmitted to human from birds. The neuraminidase (NA) gene plays an important role the release and spread of the virus from infected cells and throughout the bird. The complete nucleotide sequences of the NA gene of seven H9N2 viruses collected from apparent healthy chicken and quail flocks in Egypt during 2014-2015, were amplified and sequenced. The phylogenetic relationships were investigated and all viruses were belonging to the A/Q/HK/G1/97 strain (G1-like). There were no insertions or deletions or shortening in NA stalk regions when compared to Y280-lineage and the human H9N2 isolates. No obvious changes NA interactions with antiviral drugs. We found that the Egyptian H9N2 viruses have seven glycosylation sites like the most recorded H9N2 viruses in the country, except A/Q/Egypt/14864V/2014 virus which has only six. The NA has four amino acid substitutions distributed in different parts of the hemadsorbing site. The most characteristic substitutions in this site were S372A and W403R these substitutions were a distinctive feature resembling to human H9N2, H2N2 and H3N2 viruses but differs from the other avian influenza viruses. These Special features of surface glycoproteins of LPAI-H9N2 viruses refer to the tendency for enhanced introductions into humans and ensuring the importance of poultry in the transfer influenza viruses.
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Affiliation(s)
- Zienab Mosaad
- National Laboratory for Veterinary Quality Control on Poultry Production, Animal Health Research Institute, P.O. Box 264, Dokki, Giza, 12618 Egypt
| | - Abdelsatar Arafa
- National Laboratory for Veterinary Quality Control on Poultry Production, Animal Health Research Institute, P.O. Box 264, Dokki, Giza, 12618 Egypt
| | - Hussein A Hussein
- Virology Department, Faculty of Veterinary Medicine, Cairo University, Giza, 12211 Egypt
| | - Mohamed A Shalaby
- Virology Department, Faculty of Veterinary Medicine, Cairo University, Giza, 12211 Egypt
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Camp JV, Jonsson CB. A Role for Neutrophils in Viral Respiratory Disease. Front Immunol 2017; 8:550. [PMID: 28553293 PMCID: PMC5427094 DOI: 10.3389/fimmu.2017.00550] [Citation(s) in RCA: 167] [Impact Index Per Article: 20.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2016] [Accepted: 04/24/2017] [Indexed: 12/23/2022] Open
Abstract
Neutrophils are immune cells that are well known to be present during many types of lung diseases associated with acute respiratory distress syndrome (ARDS) and may contribute to acute lung injury. Neutrophils are poorly studied with respect to viral infection, and specifically to respiratory viral disease. Influenza A virus (IAV) infection is the cause of a respiratory disease that poses a significant global public health concern. Influenza disease presents as a relatively mild and self-limiting although highly pathogenic forms exist. Neutrophils increase in the respiratory tract during infection with mild seasonal IAV, moderate and severe epidemic IAV infection, and emerging highly pathogenic avian influenza (HPAI). During severe influenza pneumonia and HPAI infection, the number of neutrophils in the lower respiratory tract is correlated with disease severity. Thus, comparative analyses of the relationship between IAV infection and neutrophils provide insights into the relative contribution of host and viral factors that contribute to disease severity. Herein, we review the contribution of neutrophils to IAV disease pathogenesis and to other respiratory virus infections.
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Affiliation(s)
- Jeremy V Camp
- Institute of Virology, University of Veterinary Medicine at Vienna, Vienna, Austria
| | - Colleen B Jonsson
- Department of Microbiology, University of Tennessee-Knoxville, Knoxville, TN, USA
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Hong KH. Viral Infections in Workers in Hospital and Research Laboratory Settings. ANNALS OF CLINICAL MICROBIOLOGY 2017. [DOI: 10.5145/acm.2017.20.2.27] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Affiliation(s)
- Ki Ho Hong
- Department of Laboratory Medicine, Seoul Medical Center, Seoul, Korea
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Ivanova VT, Garina EO, Burtseva EI, Kirillova ES, Ivanova MV, Stejskal J, Sapurina IY. Conducting polymers as sorbents of influenza viruses. CHEMICAL PAPERS 2016. [DOI: 10.1007/s11696-016-0068-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
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Glycan-protein interactions in viral pathogenesis. Curr Opin Struct Biol 2016; 40:153-162. [PMID: 27792989 PMCID: PMC5526076 DOI: 10.1016/j.sbi.2016.10.003] [Citation(s) in RCA: 90] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Accepted: 10/01/2016] [Indexed: 12/24/2022]
Abstract
The surfaces of host cells and viruses are decorated by complex glycans, which play multifaceted roles in the dynamic interplay between the virus and the host including viral entry into host cell, modulation of proteolytic cleavage of viral proteins, recognition and neutralization of virus by host immune system. These roles are mediated by specific multivalent interactions of glycans with their cognate proteins (generally termed as glycan-binding proteins or GBPs or lectins). The advances in tools and technologies to chemically synthesize and structurally characterize glycans and glycan-GBP interactions have offered several insights into the role of glycan-GBP interactions in viral pathogenesis and have presented opportunities to target these interactions for novel antiviral therapeutic or vaccine strategies. This review covers aspects of role of host cell surface glycan receptors and viral surface glycans in viral pathogenesis and offers perspectives on how to employ various analytical tools to target glycan-GBP interactions.
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Dalziel AE, Delean S, Heinrich S, Cassey P. Persistence of Low Pathogenic Influenza A Virus in Water: A Systematic Review and Quantitative Meta-Analysis. PLoS One 2016; 11:e0161929. [PMID: 27736884 PMCID: PMC5063340 DOI: 10.1371/journal.pone.0161929] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Accepted: 08/15/2016] [Indexed: 11/21/2022] Open
Abstract
Avian influenza viruses are able to persist in the environment, in-between the transmission of the virus among its natural hosts. Quantifying the environmental factors that affect the persistence of avian influenza virus is important for influencing our ability to predict future outbreaks and target surveillance and control methods. We conducted a systematic review and quantitative meta-analysis of the environmental factors that affect the decay of low pathogenic avian influenza virus (LPAIV) in water. Abiotic factors affecting the persistence of LPAIV have been investigated for nearly 40 years, yet published data was produced by only 26 quantitative studies. These studies have been conducted by a small number of principal authors (n = 17) and have investigated a narrow range of environmental conditions, all of which were based in laboratories with limited reflection of natural conditions. The use of quantitative meta-analytic techniques provided the opportunity to assess persistence across a greater range of conditions than each individual study can achieve, through the estimation of mean effect-sizes and relationships among multiple variables. Temperature was the most influential variable, for both the strength and magnitude of the effect-size. Moderator variables explained a large proportion of the heterogeneity among effect-sizes. Salinity and pH were important factors, although future work is required to broaden the range of abiotic factors examined, as well as including further diurnal variation and greater environmental realism generally. We were unable to extract a quantitative effect-size estimate for approximately half (50.4%) of the reported experimental outcomes and we strongly recommend a minimum set of quantitative reporting to be included in all studies, which will allow robust assimilation and analysis of future findings. In addition we suggest possible means of increasing the applicability of future studies to the natural environment, and evaluating the biological content of natural waterbodies.
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Affiliation(s)
- Antonia E. Dalziel
- School of Biological Sciences, The University of Adelaide, Adelaide, South Australia
| | - Steven Delean
- School of Biological Sciences, The University of Adelaide, Adelaide, South Australia
| | - Sarah Heinrich
- School of Biological Sciences, The University of Adelaide, Adelaide, South Australia
| | - Phillip Cassey
- School of Biological Sciences, The University of Adelaide, Adelaide, South Australia
- Centre for Conservation Science & Technology, The University of Adelaide, Adelaide, South Australia
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Patel GP, Crank CW, Black S. Therapeutic Interventions for the Treatment and Control of Influenza. J Pharm Technol 2016. [DOI: 10.1177/875512250702300204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Objective:To review antiviral management of influenza and discuss recent developments in antiviral resistance.Data Sources:Literature retrieval was accessed through MEDLINE/PubMed (1977–February 2007) using the terms influenza, resistance, adamantanes, and neuraminidase inhibitors, treatment, and prevention. In addition, reference citations from identified publications were reviewed.Study Selection and Data Extraction:All articles in English identified from the data sources were evaluated.Data Synthesis:Infection with influenza is associated with 36,000 deaths and more than 200,000 hospitalizations in the US each year and results in a large economic burden on society. We reviewed 7 trials describing management of influenza; the results showed that 92% of influenza cases demonstrated adamantane resistance in 2005. Selection of treatment for influenza with a neuraminidase inhibitor should be based on patient preference, past medical history, and managed care restrictions since one agent has not demonstrated superiority. Early initiation of treatment, within 12 hours of symptom onset (compared with 48 h), has resulted in illness being shortened by more than 3 days. Conclusions shown in the trials reviewed here regarding the consequences of increasing incidence of influenza A resistance include: viral surveillance cultures are important, influenza has a significant global impact, and inappropriate use of antiinfective agents results in local and global resistance.Conclusions:Therapeutic options for the management of influenza include the neuraminidase inhibitors, zanamavir and oseltamivir. Unfortunately, new classes of antiviral drugs for influenza will not be forthcoming in the near future. Adamantane resistance is now commonly demonstrated in influenza. At this time, efforts should be made to minimize patient risk for infection.
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Affiliation(s)
- Gourang P Patel
- GOURANG P PATEL PharmD BCPS, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Rush University Medical Center and Rush Medical College, Chicago, IL
| | - Christopher W Crank
- CHRISTOPHER W CRANK PharmD BCPS, Section of Infectious Disease, Department of Internal Medicine, Rush University Medical Center and Rush Medical College
| | - Stephanie Black
- STEPHANIE BLACK MD, Section of Infectious Disease, Department of Internal Medicine, Rush University Medical Center and Rush Medical College
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Bat-man disease transmission: zoonotic pathogens from wildlife reservoirs to human populations. Cell Death Discov 2016; 2:16048. [PMID: 27551536 PMCID: PMC4979447 DOI: 10.1038/cddiscovery.2016.48] [Citation(s) in RCA: 107] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2016] [Accepted: 05/25/2016] [Indexed: 12/11/2022] Open
Abstract
Bats are natural reservoir hosts and sources of infection of several microorganisms, many of which cause severe human diseases. Because of contact between bats and other animals, including humans, the possibility exists for additional interspecies transmissions and resulting disease outbreaks. The purpose of this article is to supply an overview on the main pathogens isolated from bats that have the potential to cause disease in humans.
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50
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Das A, Suarez DL. Development and Bench Validation of Real-Time Reverse Transcription Polymerase Chain Reaction Protocols for Rapid Detection of the Subtypes H6, H9, and H11 of Avian Influenza Viruses in Experimental Samples. J Vet Diagn Invest 2016; 19:625-34. [DOI: 10.1177/104063870701900603] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Real-time reverse transcription polymerase chain reaction (RRT-PCR) is commonly used for the rapid detection, as well as to determine the subtype, of avian influenza viruses (AIVs). There are 16 known serologically distinct hemagglutinin (HA) subtypes of AIV described. Currently, determination of the subtypes of AIVs by RRT-PCR tests has been limited to the H5 and H7 subtypes. In this study, RRT-PCR assays were developed in simplex formats for rapid detection of AIV subtypes H6, H9, and H11. The primers and probes for RRT-PCR were designed from nucleotide sequences of the HA genes, which were either downloaded from GenBank (for H6 and H9) or sequenced for this study. The specificity and sensitivity of the RRT-PCR assays were determined based on the detection of the virus from a proficiency panel consisting of 15 different HA subtypes of AIVs and from serial dilutions of target viral RNA. The subtype-specific RRT-PCR assays were used to detect the virus in cloacal and oropharyngeal swabs of experimental chickens inoculated with H6, H9, and H11 AIVs, and the test results were compared with validated RRT-PCR assays based on the amplification of AI matrix (MA) gene. A high correlation of the matrix test and the specific H6, H9, and H11 by the RRT-PCR assays was observed; kappa coefficients for the agreement of test results in cloacal and oropharyngeal swabs combined were 0.927, 0.962, and 0.981, respectively.
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Affiliation(s)
- Amaresh Das
- From the Southeast Poultry Research Laboratory, Agricultural Research Service, USDA, Athens, GA
| | - David L. Suarez
- From the Southeast Poultry Research Laboratory, Agricultural Research Service, USDA, Athens, GA
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