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Fiske KL, Brigleb PH, Sanchez LM, Hinterleitner R, Taylor GM, Dermody TS. Strain-specific differences in reovirus infection of murine macrophages segregate with polymorphisms in viral outer-capsid protein σ3. J Virol 2024; 98:e0114724. [PMID: 39431846 PMCID: PMC11575339 DOI: 10.1128/jvi.01147-24] [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: 06/28/2024] [Accepted: 09/22/2024] [Indexed: 10/22/2024] Open
Abstract
Mammalian orthoreovirus (reovirus) strains type 1 Lang (T1L) and type 3 Dearing-RV (T3D-RV) infect the intestine in mice but differ in the induction of inflammatory responses. T1L infection is associated with the blockade of oral immunological tolerance to newly introduced dietary antigens, whereas T3D-RV is not. T1L infection leads to an increase in infiltrating phagocytes, including macrophages, in gut-associated lymphoid tissues that are not observed in T3D-RV infection. However, the function of macrophages in reovirus intestinal infection is unknown. Using cells sorted from infected intestinal tissue and primary cultures of bone-marrow-derived macrophages (BMDMs), we discovered that T1L infects macrophages more efficiently than T3D-RV. Analysis of T1L × T3D-RV reassortant viruses revealed that the viral S4 gene segment, which encodes outer-capsid protein σ3, is responsible for strain-specific differences in infection of BMDMs. Differences in the binding of T1L and T3D-RV to BMDMs also segregated with the σ3-encoding S4 gene. Paired immunoglobulin-like receptor B (PirB), which serves as a receptor for reovirus, is expressed on macrophages and engages σ3. We found that PirB-specific antibody blocks T1L binding to BMDMs and that T1L binding to PirB-/- BMDMs is significantly diminished. Collectively, our data suggest that reovirus T1L infection of macrophages is dependent on engagement of PirB by viral outer-capsid protein σ3. These findings raise the possibility that macrophages function in the innate immune response to reovirus infection that blocks immunological tolerance to new food antigens.IMPORTANCEMammalian orthoreovirus (reovirus) infects humans throughout their lifespan and has been linked to celiac disease (CeD). CeD is caused by a loss of oral immunological tolerance (LOT) to dietary gluten and leads to intestinal inflammation following gluten ingestion, which worsens with prolonged exposure and can cause malnutrition. There are limited treatment options for CeD. While there are genetic risk factors associated with the illness, triggers for disease onset are not completely understood. Enteric viruses, including reovirus, have been linked to CeD induction. We found that a reovirus strain associated with oral immunological tolerance blockade infects macrophages by virtue of its capacity to bind macrophage receptor PirB. These data contribute to an understanding of the innate immune response elicited by reovirus, which may shed light on how viruses trigger LOT and inform the development of CeD vaccines and therapeutic agents.
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Affiliation(s)
- Kay L Fiske
- Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- Institute of Infection, Inflammation, and Immunity, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Pamela H Brigleb
- Institute of Infection, Inflammation, and Immunity, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Luzmariel Medina Sanchez
- Institute of Infection, Inflammation, and Immunity, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- Graduate Program in Microbiology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Reinhard Hinterleitner
- Institute of Infection, Inflammation, and Immunity, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Gwen M Taylor
- Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- Institute of Infection, Inflammation, and Immunity, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Terence S Dermody
- Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- Institute of Infection, Inflammation, and Immunity, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
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Hakim MS, Gazali FM, Widyaningsih SA, Parvez MK. Driving forces of continuing evolution of rotaviruses. World J Virol 2024; 13:93774. [PMID: 38984077 PMCID: PMC11229848 DOI: 10.5501/wjv.v13.i2.93774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 05/06/2024] [Accepted: 05/17/2024] [Indexed: 06/24/2024] Open
Abstract
Rotaviruses are non-enveloped double-stranded RNA virus that causes acute diarrheal diseases in children (< 5 years). More than 90% of the global rotavirus infection in humans was caused by Rotavirus group A. Rotavirus infection has caused more than 200000 deaths annually and predominantly occurs in the low-income countries. Rotavirus evolution is indicated by the strain dynamics or the emergence of the unprecedented strain. The major factors that drive the rotavirus evolution include the genetic shift that is caused by the reassortment mechanism, either in the intra- or the inter-genogroup. However, other factors are also known to have an impact on rotavirus evolution. This review discusses the structure and types, epidemiology, and evolution of rotaviruses. This article also reviews other supplemental factors of rotavirus evolution, such as genetic reassortment, mutation rate, glycan specificity, vaccine introduction, the host immune responses, and antiviral drugs.
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Affiliation(s)
- Mohamad Saifudin Hakim
- Postgraduate School of Molecular Medicine, Erasmus MC-University Medical Center, Rotterdam 3015GD, Netherlands
- Viral Infection Working Group, International Society of Antimicrobial Chemotherapy, London EC4R 9AN, United Kingdom
| | - Faris Muhammad Gazali
- Master Program in Biotechnology, Postgraduate School, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia
| | - Suci Ardini Widyaningsih
- Master of Medical Sciences in Clinical Investigation, Harvard Medical School, Boston, MA 02115, United States
| | - Mohammad Khalid Parvez
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia
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Zhao C, Chen S, Han Y, Zhang F, Ren M, Hu Q, Ye P, Li X, Jin E, Li S. Proteomic Analysis of Rat Duodenum Reveals the Modulatory Effect of Boron Supplementation on Immune Activity. Genes (Basel) 2023; 14:1560. [PMID: 37628612 PMCID: PMC10454175 DOI: 10.3390/genes14081560] [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: 06/14/2023] [Revised: 07/23/2023] [Accepted: 07/26/2023] [Indexed: 08/27/2023] Open
Abstract
The proper supplementation of boron, an essential trace element, can enhance animal immune function. We utilized the method of TMT peptide labeling in conjunction with LC-MS/MS quantitative proteomics for the purpose of examining the effects of boric acid on a rat model and analyzing proteins from the duodenum. In total, 5594 proteins were obtained from the 0, 10, and 320 mg/L boron treatment groups. Two hundred eighty-four proteins that exhibit differential expression were detected. Among the comparison, groups of 0 vs. 10 mg/L, 0 vs. 320 mg/L, and 10 vs. 320 mg/L of boron, 110, 32, and 179 proteins, respectively, demonstrated differential expression. The results revealed that these differential expression proteins (DEPs) mainly clustered into two profiles. GO annotations suggested that most of the DEPs played a role in the immune system process, in which 2'-5'-oligoadenylate synthetase-like, myxovirus resistance 1, myxovirus resistance 2, dynein cytoplasmic 1 intermediate chain 1, and coiled-coil domain containing 88B showed differential expression. The DEPs had demonstrated an augmentation in the signaling pathways, which primarily include phagosome, antigen processing, and presentation, as well as cell adhesion molecules (CAMs). Our study found that immune responses in the duodenum were enhanced by lower doses of boron and that this effect is likely mediated by changes in protein expression patterns in related signaling pathways. It offers an in-depth understanding of the underlying molecular mechanisms that lead to immune modulation in rats subjected to dietary boron treatment.
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Affiliation(s)
- Chunfang Zhao
- College of Animal Science, Anhui Science and Technology University, No. 9 Donghua Road, Fengyang County, Chuzhou 233100, China; (C.Z.); (S.C.); (Y.H.); (F.Z.); (M.R.); (Q.H.); (P.Y.); (X.L.); (S.L.)
- Anhui Province Key Laboratory of Animal Nutritional Regulation and Health, No. 9 Donghua Road, Fengyang County, Chuzhou 233100, China
| | - Shuqin Chen
- College of Animal Science, Anhui Science and Technology University, No. 9 Donghua Road, Fengyang County, Chuzhou 233100, China; (C.Z.); (S.C.); (Y.H.); (F.Z.); (M.R.); (Q.H.); (P.Y.); (X.L.); (S.L.)
- Anhui Province Key Laboratory of Animal Nutritional Regulation and Health, No. 9 Donghua Road, Fengyang County, Chuzhou 233100, China
| | - Yujiao Han
- College of Animal Science, Anhui Science and Technology University, No. 9 Donghua Road, Fengyang County, Chuzhou 233100, China; (C.Z.); (S.C.); (Y.H.); (F.Z.); (M.R.); (Q.H.); (P.Y.); (X.L.); (S.L.)
- Anhui Province Key Laboratory of Animal Nutritional Regulation and Health, No. 9 Donghua Road, Fengyang County, Chuzhou 233100, China
| | - Feng Zhang
- College of Animal Science, Anhui Science and Technology University, No. 9 Donghua Road, Fengyang County, Chuzhou 233100, China; (C.Z.); (S.C.); (Y.H.); (F.Z.); (M.R.); (Q.H.); (P.Y.); (X.L.); (S.L.)
- Anhui Province Key Laboratory of Animal Nutritional Regulation and Health, No. 9 Donghua Road, Fengyang County, Chuzhou 233100, China
| | - Man Ren
- College of Animal Science, Anhui Science and Technology University, No. 9 Donghua Road, Fengyang County, Chuzhou 233100, China; (C.Z.); (S.C.); (Y.H.); (F.Z.); (M.R.); (Q.H.); (P.Y.); (X.L.); (S.L.)
- Anhui Province Key Laboratory of Animal Nutritional Regulation and Health, No. 9 Donghua Road, Fengyang County, Chuzhou 233100, China
| | - Qianqian Hu
- College of Animal Science, Anhui Science and Technology University, No. 9 Donghua Road, Fengyang County, Chuzhou 233100, China; (C.Z.); (S.C.); (Y.H.); (F.Z.); (M.R.); (Q.H.); (P.Y.); (X.L.); (S.L.)
- Anhui Province Key Laboratory of Animal Nutritional Regulation and Health, No. 9 Donghua Road, Fengyang County, Chuzhou 233100, China
| | - Pengfei Ye
- College of Animal Science, Anhui Science and Technology University, No. 9 Donghua Road, Fengyang County, Chuzhou 233100, China; (C.Z.); (S.C.); (Y.H.); (F.Z.); (M.R.); (Q.H.); (P.Y.); (X.L.); (S.L.)
- Anhui Province Key Laboratory of Animal Nutritional Regulation and Health, No. 9 Donghua Road, Fengyang County, Chuzhou 233100, China
| | - Xiaojin Li
- College of Animal Science, Anhui Science and Technology University, No. 9 Donghua Road, Fengyang County, Chuzhou 233100, China; (C.Z.); (S.C.); (Y.H.); (F.Z.); (M.R.); (Q.H.); (P.Y.); (X.L.); (S.L.)
- Anhui Province Key Laboratory of Animal Nutritional Regulation and Health, No. 9 Donghua Road, Fengyang County, Chuzhou 233100, China
| | - Erhui Jin
- College of Animal Science, Anhui Science and Technology University, No. 9 Donghua Road, Fengyang County, Chuzhou 233100, China; (C.Z.); (S.C.); (Y.H.); (F.Z.); (M.R.); (Q.H.); (P.Y.); (X.L.); (S.L.)
- Anhui Province Key Laboratory of Animal Nutritional Regulation and Health, No. 9 Donghua Road, Fengyang County, Chuzhou 233100, China
| | - Shenghe Li
- College of Animal Science, Anhui Science and Technology University, No. 9 Donghua Road, Fengyang County, Chuzhou 233100, China; (C.Z.); (S.C.); (Y.H.); (F.Z.); (M.R.); (Q.H.); (P.Y.); (X.L.); (S.L.)
- Anhui Province Key Laboratory of Animal Nutritional Regulation and Health, No. 9 Donghua Road, Fengyang County, Chuzhou 233100, China
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Kumar D, Shepherd FK, Springer NL, Mwangi W, Marthaler DG. Rotavirus Infection in Swine: Genotypic Diversity, Immune Responses, and Role of Gut Microbiome in Rotavirus Immunity. Pathogens 2022; 11:pathogens11101078. [PMID: 36297136 PMCID: PMC9607047 DOI: 10.3390/pathogens11101078] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 09/13/2022] [Accepted: 09/17/2022] [Indexed: 11/16/2022] Open
Abstract
Rotaviruses (RVs) are endemic in swine populations, and all swine herds certainly have a history of RV infection and circulation. Rotavirus A (RVA) and C (RVC) are the most common among all RV species reported in swine. RVA was considered most prevalent and pathogenic in swine; however, RVC has been emerging as a significant cause of enteritis in newborn piglets. RV eradication from swine herds is not practically achievable, hence producers’ mainly focus on minimizing the production impact of RV infections by reducing mortality and diarrhea. Since no intra-uterine passage of immunoglobulins occur in swine during gestation, newborn piglets are highly susceptible to RV infection at birth. Boosting lactogenic immunity in gilts by using vaccines and natural planned exposure (NPE) is currently the only way to prevent RV infections in piglets. RVs are highly diverse and multiple RV species have been reported from swine, which also contributes to the difficulties in preventing RV diarrhea in swine herds. Human RV-gut microbiome studies support a link between microbiome composition and oral RV immunogenicity. Such information is completely lacking for RVs in swine. It is not known how RV infection affects the functionality or structure of gut microbiome in swine. In this review, we provide a detailed overview of genotypic diversity of swine RVs, host-ranges, innate and adaptive immune responses to RVs, homotypic and heterotypic immunity to RVs, current methods used for RV management in swine herds, role of maternal immunity in piglet protection, and prospects of investigating swine gut microbiota in providing immunity against rotaviruses.
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Affiliation(s)
- Deepak Kumar
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA
- Correspondence: (D.K.); (W.M.); (D.G.M.); Tel.: +1-804-503-1241 (D.K.)
| | - Frances K Shepherd
- Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55108, USA
| | - Nora L. Springer
- Clinical Pathology, Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA
| | - Waithaka Mwangi
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA
- Correspondence: (D.K.); (W.M.); (D.G.M.); Tel.: +1-804-503-1241 (D.K.)
| | - Douglas G. Marthaler
- Indical Inc., 1317 Edgewater Dr #3722, Orlando, FL 32804, USA
- Correspondence: (D.K.); (W.M.); (D.G.M.); Tel.: +1-804-503-1241 (D.K.)
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Peer V, Schwartz N, Green MS. A Pooled Analysis of Sex Differences in Rotaviral Enteritis Incidence Rates in Three Countries Over Different Time Periods. WOMEN'S HEALTH REPORTS 2022; 3:228-237. [PMID: 35262061 PMCID: PMC8896211 DOI: 10.1089/whr.2021.0096] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Accepted: 01/19/2022] [Indexed: 12/13/2022]
Abstract
Background: Sex differences in incidence rates (IRs) of infectious diseases could provide clues to the mechanisms of infection. The results of studies on sex differences in the incidence of rotaviral enteritis have been inconsistent. Methods: We carried out a pooled analysis of sex differences in IRs for rotaviral enteritis in three countries for a period of 7–22 years. Male-to-female incidence rate ratios (IRRs) were computed by age group, country, and years of reporting. A meta-analytic methodology was used to combine IRRs. Metaregression was performed to evaluate the contribution of age group, country, and years of reporting to the IRR. Results: Significantly higher IRs in males were found in the age groups 0–4, 5–9, and 10–14 years, with pooled IRRs (with 95% confidence intervals [CIs]) of 1.12 (1.09–1.14), 1.07 (1.05–1.09), and 1.13 (1.05–1.21), respectively. In adults, the sex differences were reversed with higher rates in females. The pooled male-to-female IRRs (with 95% CIs) were 0.66 (0.64–0.68), 0.78 (0.72–0.85), and 0.78 (0.72–0.84) for the age groups 15–44, 45–64, and 65+ years, respectively. Metaregression results demonstrated that age is responsible for much of the variation in IRRs. Conclusions: The higher rotaviral enteritis IRs in males at a very early age suggest that sex-related factors unrelated to exposure may play a role. The higher IRs in adult females could result, at least partly, from behavioral and occupational factors.
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Affiliation(s)
- Victoria Peer
- School of Public Health, University of Haifa, Haifa, Israel
| | - Naama Schwartz
- School of Public Health, University of Haifa, Haifa, Israel
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Abstract
Abstract
Viruses completely rely on the energy and metabolic systems of host cells for life activities. Viral infections usually lead to cytopathic effects and host diseases. To date, there are still no specific clinical vaccines or drugs against most viral infections. Therefore, understanding the molecular and cellular mechanisms of viral infections is of great significance to prevent and treat viral diseases. A variety of viral infections are related to the p38 MAPK signalling pathway, and p38 is an important host factor in virus-infected cells. Here, we introduce the different signalling pathways of p38 activation and then summarise how different viruses induce p38 phosphorylation. Finally, we provide a general summary of the effect of p38 activation on virus replication. Our review provides integrated data on p38 activation and viral infections and describes the potential application of targeting p38 as an antiviral strategy.
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Elean M, Albarracin L, Fukuyama K, Zhou B, Tomokiyo M, Kitahara S, Araki S, Suda Y, Saavedra L, Villena J, Hebert EM, Kitazawa H. Lactobacillus delbrueckii CRL 581 Differentially Modulates TLR3-Triggered Antiviral Innate Immune Response in Intestinal Epithelial Cells and Macrophages. Microorganisms 2021; 9:microorganisms9122449. [PMID: 34946051 PMCID: PMC8704909 DOI: 10.3390/microorganisms9122449] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 11/17/2021] [Accepted: 11/25/2021] [Indexed: 11/16/2022] Open
Abstract
Lactobacillus delbrueckii subsp. lactis CRL 581 beneficially modulates the intestinal antiviral innate immune response triggered by the Toll-like receptor 3 (TLR3) agonist poly(I:C) in vivo. This study aimed to characterize further the immunomodulatory properties of the technologically relevant starter culture L. delbrueckii subsp. lactis CRL 581 by evaluating its interaction with intestinal epithelial cells and macrophages in the context of innate immune responses triggered by TLR3. Our results showed that the CRL 581 strain was able to adhere to porcine intestinal epithelial (PIE) cells and mucins. The CRL 581 strain also augmented the expression of antiviral factors (IFN-α, IFN-β, Mx1, OAS1, and OAS2) and reduced inflammatory cytokines in PIE cells triggered by TLR3 stimulation. In addition, the influence of L. delbrueckii subsp. lactis CRL 581 on the response of murine RAW macrophages to the activation of TLR3 was evaluated. The CRL 581 strain was capable of enhancing the expression of IFN-α, IFN-β, IFN-γ, Mx1, OAS1, TNF-α, and IL-1β. Of note, the CRL 581 strain also augmented the expression of IL-10 in macrophages. The results of this study show that the high proteolytic strain L. delbrueckii spp. lactis CRL 581 was able to beneficially modulate the intestinal innate antiviral immune response by regulating the response of both epithelial cells and macrophages relative to TLR3 activation.
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Affiliation(s)
- Mariano Elean
- Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman 4000, Argentina; (M.E.); (L.A.); (L.S.)
| | - Leonardo Albarracin
- Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman 4000, Argentina; (M.E.); (L.A.); (L.S.)
| | - Kohtaro Fukuyama
- Laboratory of Animal Food Function, Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan; (K.F.); (B.Z.); (M.T.); (S.K.); (S.A.)
| | - Binghui Zhou
- Laboratory of Animal Food Function, Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan; (K.F.); (B.Z.); (M.T.); (S.K.); (S.A.)
- International Education and Research Center for Food Agricultural Immunology (CFAI), Livestock Immunology Unit, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan
| | - Mikado Tomokiyo
- Laboratory of Animal Food Function, Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan; (K.F.); (B.Z.); (M.T.); (S.K.); (S.A.)
- International Education and Research Center for Food Agricultural Immunology (CFAI), Livestock Immunology Unit, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan
| | - Shugo Kitahara
- Laboratory of Animal Food Function, Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan; (K.F.); (B.Z.); (M.T.); (S.K.); (S.A.)
| | - Shota Araki
- Laboratory of Animal Food Function, Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan; (K.F.); (B.Z.); (M.T.); (S.K.); (S.A.)
| | - Yoshihito Suda
- Department of Food, Agriculture and Environment, Miyagi University, Sendai 980-8572, Japan;
| | - Lucila Saavedra
- Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman 4000, Argentina; (M.E.); (L.A.); (L.S.)
| | - Julio Villena
- Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman 4000, Argentina; (M.E.); (L.A.); (L.S.)
- Laboratory of Animal Food Function, Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan; (K.F.); (B.Z.); (M.T.); (S.K.); (S.A.)
- Correspondence: (J.V.); (E.M.H.); (H.K.)
| | - Elvira M. Hebert
- Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman 4000, Argentina; (M.E.); (L.A.); (L.S.)
- Correspondence: (J.V.); (E.M.H.); (H.K.)
| | - Haruki Kitazawa
- Laboratory of Animal Food Function, Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan; (K.F.); (B.Z.); (M.T.); (S.K.); (S.A.)
- International Education and Research Center for Food Agricultural Immunology (CFAI), Livestock Immunology Unit, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan
- Correspondence: (J.V.); (E.M.H.); (H.K.)
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Liu N, Meng B, Zeng L, Yin S, Hu Y, Li S, Fu Y, Zhang X, Xie C, Shu L, Yang M, Wang Y, Yang X. Discovery of a novel rice-derived peptide with significant anti-gout potency. Food Funct 2020; 11:10542-10553. [PMID: 33185232 DOI: 10.1039/d0fo01774d] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
As a metabolic disease, gout, which seriously affects the normal life of patients, has become increasingly common in modern society. However, the existing medicines cannot completely meet the clinical needs. In the current study, a novel short peptide (named rice-derived-peptide-2 (RDP2), AAAAGAMPK-NH2, 785.97 Da) was isolated and identified from water extract of shelled Oryza sativa fruits, without toxic side effects but excellent stability. Our results indicated that RDP2 (the minimum effective concentration is 5 μg kg-1) induced a significant reduction in serum uric acid levels in hyperuricemic mice via suppressing xanthine oxidase activity and urate transporter 1 expression, as well as alleviated renal damage through inhibiting the activation of NLRP3 inflammasome. In addition, RDP2 can also alleviate paw swelling and inflammatory reactions in mice after subcutaneous injection of monosodium urate crystals. As mentioned above, we obtained a novel peptide which could work through all stages of gout, not only reducing uric acid levels and renal damage in hyperuricemic mice, but also alleviating inflammatory responses associated with acute gout attack, and thus provided a new peptide molecular template for the development of anti-gout drugs.
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Affiliation(s)
- Naixin Liu
- Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan 650500, China.
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Liu N, Wang Y, Zeng L, Yin S, Hu Y, Li S, Fu Y, Zhang X, Xie C, Shu L, Li Y, Sun H, Yang M, Sun J, Yang X. RDP3, A Novel Antigout Peptide Derived from Water Extract of Rice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:7143-7151. [PMID: 32543191 DOI: 10.1021/acs.jafc.0c02535] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Gout and hyperuricemia can seriously affect the quality of life; at present, however, existing medicines are unable to meet all clinical needs. In the current study, a novel peptide (i.e., rice-derived-peptide-3 (RDP3), AAAAMAGPK-NH2, 785.97 Da) in water extract obtained from shelled Oryza sativa fruits was identified. Testing revealed that RDP3 (minimum effective concentration 100 μg/kg) did not show both hemolytic and acute toxicity, and reduced uric acid levels in the serum of hyperuricemic mice by inhibiting xanthine oxidase activity and decreasing urate transporter 1 expression. RDP3 also alleviated renal injury in hyperuricemic mice by decreasing NLRP3 inflammasome expression. Furthermore, RDP3 alleviated formalin-induced paw pain and reduced monosodium urate crystal-induced paw swelling and inflammatory factors in mice. Thus, this newly identified peptide reduced uric acid levels and renal damage in hyperuricemic mice and showed anti-inflammatory and analgesic activities, indicating the potential of RDP3 as an antigout medicine candidate.
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Affiliation(s)
- Naixin Liu
- Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, Yunnan, China
| | - Ying Wang
- Key Laboratory of Chemistry in Ethnic Medicine Resource, State Ethnic Affairs Commission & Ministry of Education, School of Ethno-Medicine and Ethno-Pharmacy, Yunnan Minzu University, Kunming 650504, Yunnan, China
| | - Lin Zeng
- Public Technical Service Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China
| | - Saige Yin
- Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, Yunnan, China
| | - Yan Hu
- Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, Yunnan, China
| | - Shanshan Li
- Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, Yunnan, China
| | - Yang Fu
- Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, Yunnan, China
| | - Xinping Zhang
- Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, Yunnan, China
| | - Chun Xie
- Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, Yunnan, China
| | - Longjun Shu
- Key Laboratory of Chemistry in Ethnic Medicine Resource, State Ethnic Affairs Commission & Ministry of Education, School of Ethno-Medicine and Ethno-Pharmacy, Yunnan Minzu University, Kunming 650504, Yunnan, China
| | - Yilin Li
- Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, Yunnan, China
| | - Huiling Sun
- Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, Yunnan, China
| | - Meifeng Yang
- Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, Yunnan, China
| | - Jun Sun
- Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, Yunnan, China
| | - Xinwang Yang
- Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, Yunnan, China
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10
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Zhou Y, Qiao H, Yin N, Chen L, Xie Y, Wu J, Du J, Lin X, Wang Y, Liu Y, Yi S, Zhang G, Sun M, He Z, Li H. Immune and cytokine/chemokine responses of PBMCs in rotavirus‐infected rhesus infants and their significance in viral pathogenesis. J Med Virol 2019; 91:1448-1469. [DOI: 10.1002/jmv.25460] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Revised: 01/17/2019] [Accepted: 02/01/2019] [Indexed: 12/23/2022]
Affiliation(s)
- Yan Zhou
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on severe Infectious Disease Kunming China
| | - Hongtu Qiao
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on severe Infectious Disease Kunming China
| | - Na Yin
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on severe Infectious Disease Kunming China
| | - Linlin Chen
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on severe Infectious Disease Kunming China
| | - Yuping Xie
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on severe Infectious Disease Kunming China
| | - Jinyuan Wu
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on severe Infectious Disease Kunming China
| | - Jing Du
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on severe Infectious Disease Kunming China
| | - Xiaochen Lin
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on severe Infectious Disease Kunming China
| | - Yi Wang
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on severe Infectious Disease Kunming China
| | - Yang Liu
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on severe Infectious Disease Kunming China
| | - Shan Yi
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on severe Infectious Disease Kunming China
| | - Guangming Zhang
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on severe Infectious Disease Kunming China
| | - Maosheng Sun
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on severe Infectious Disease Kunming China
| | - Zhanlong He
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on severe Infectious Disease Kunming China
| | - Hongjun Li
- Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on severe Infectious Disease Kunming China
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11
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Sadiq A, Bostan N, Yinda KC, Naseem S, Sattar S. Rotavirus: Genetics, pathogenesis and vaccine advances. Rev Med Virol 2018; 28:e2003. [PMID: 30156344 DOI: 10.1002/rmv.2003] [Citation(s) in RCA: 75] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Revised: 07/02/2018] [Accepted: 07/07/2018] [Indexed: 01/27/2023]
Abstract
Since its discovery 40 years ago, rotavirus (RV) is considered to be a major cause of infant and childhood morbidity and mortality particularly in developing countries. Nearly every child in the world under 5 years of age is at the risk of RV infection. It is estimated that 90% of RV-associated mortalities occur in developing countries of Africa and Asia. Two live oral vaccines, RotaTeq (RV5, Merck) and Rotarix (RV1, GlaxoSmithKline) have been successfully deployed to scale down the disease burden in Europe and America, but they are less effective in Africa and Asia. In April 2009, the World Health Organization recommended the inclusion of RV vaccination in national immunization programs of all countries with great emphasis in developing countries. To date, 86 countries have included RV vaccines into their national immunization programs including 41 Global Alliance for Vaccines and Immunization eligible countries. The predominant RV genotypes circulating all over the world are G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8], while G12[P6] and G12[P8] are emerging genotypes. On account of the segmented genome, RV shows an enormous genetic diversity that leads to the evolution of new genotypes that can influence the efficacy of current vaccines. The current need is for a global RV surveillance program to monitor the prevalence and antigenic variability of new genotypes to formulate future vaccine development planning. In this review, we will summarize the previous and recent insights into RV structure, classification, and epidemiology and current status of RV vaccination around the globe and will also cover the status of RV research and vaccine policy in Pakistan.
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Affiliation(s)
- Asma Sadiq
- Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan
| | - Nazish Bostan
- Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan
| | - Kwe Claude Yinda
- Rega Institute, Laboratory of Clinical and Epidemiological Virology, University of Leuven, Leuven, Belgium
| | - Saadia Naseem
- Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan
| | - Sadia Sattar
- Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan
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12
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Dou Y, Yim HC, Kirkwood CD, Williams BR, Sadler AJ. The innate immune receptor MDA5 limits rotavirus infection but promotes cell death and pancreatic inflammation. EMBO J 2017; 36:2742-2757. [PMID: 28851763 PMCID: PMC5599799 DOI: 10.15252/embj.201696273] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Revised: 07/25/2017] [Accepted: 07/28/2017] [Indexed: 12/31/2022] Open
Abstract
Melanoma differentiation-associated protein 5 (MDA5) mediates the innate immune response to viral infection. Polymorphisms in IFIH1, the gene coding for MDA5, correlate with the risk of developing type 1 diabetes (T1D). Here, we demonstrate that MDA5 is crucial for the immune response to enteric rotavirus infection, a proposed etiological agent for T1D. MDA5 variants encoded by minor IFIH1 alleles associated with lower T1D risk exhibit reduced activity against rotavirus infection. We find that MDA5 activity limits rotavirus infection not only through the induction of antiviral interferons and pro-inflammatory cytokines, but also by promoting cell death. Importantly, this MDA5-dependent antiviral response is specific to the pancreas of rotavirus-infected mice, similar to the autoimmunity associated with T1D. These findings imply that MDA5-induced cell death and inflammation in the pancreas facilitate progression to autoimmune destruction of pancreatic β-cells.
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Affiliation(s)
- Yu Dou
- Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Vic., Australia
- Department of Oral and Maxillofacial Surgery, Institute of Dental Medicine, Qilu Hospital of Shandong University, Jinan, China
| | - Howard Ch Yim
- Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Vic., Australia
- Department of Molecular and Translational Science, Monash University, Clayton, Vic., Australia
| | - Carl D Kirkwood
- Enteric and Diarrheal Disease, Global Health, Bill and Melinda Gates Foundation, Seattle, WA, USA
- Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Vic., Australia
| | - Bryan Rg Williams
- Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Vic., Australia
- Department of Molecular and Translational Science, Monash University, Clayton, Vic., Australia
| | - Anthony J Sadler
- Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Vic., Australia
- Department of Molecular and Translational Science, Monash University, Clayton, Vic., Australia
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13
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Albarracin L, Kobayashi H, Iida H, Sato N, Nochi T, Aso H, Salva S, Alvarez S, Kitazawa H, Villena J. Transcriptomic Analysis of the Innate Antiviral Immune Response in Porcine Intestinal Epithelial Cells: Influence of Immunobiotic Lactobacilli. Front Immunol 2017; 8:57. [PMID: 28210256 PMCID: PMC5288346 DOI: 10.3389/fimmu.2017.00057] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Accepted: 01/16/2017] [Indexed: 01/14/2023] Open
Abstract
Lactobacillus rhamnosus CRL1505 and Lactobacillus plantarum CRL1506 are immunobiotic strains able to increase protection against viral intestinal infections as demonstrated in animal models and humans. To gain insight into the host–immunobiotic interaction, the transcriptomic response of porcine intestinal epithelial (PIE) cells to the challenge with viral molecular associated pattern poly(I:C) and the changes in the transcriptomic profile induced by the immunobiotics strains CRL1505 and CRL1506 were investigated in this work. By using microarray technology and reverse transcription PCR, we obtained a global overview of the immune genes involved in the innate antiviral immune response in PIE cells. Stimulation of PIE cells with poly(I:C) significantly increased the expression of IFN-α and IFN-β, several interferon-stimulated genes, cytokines, chemokines, adhesion molecules, and genes involved in prostaglandin biosynthesis. It was also determined that lactobacilli differently modulated immune gene expression in poly(I:C)-challenged PIE cells. Most notable changes were found in antiviral factors (IFN-α, IFN-β, NPLR3, OAS1, OASL, MX2, and RNASEL) and cytokines/chemokines (IL-1β, IL-6, CCL4, CCL5, and CXCL10) that were significantly increased in lactobacilli-treated PIE cells. Immunobiotics reduced the expression of IL-15 and RAE1 genes that mediate poly(I:C) inflammatory damage. In addition, lactobacilli treatments increased the expression PLA2G4A, PTGES, and PTGS2 that are involved in prostaglandin E2 biosynthesis. L. rhamnosus CRL1505 and L. plantarum CRL1506 showed quantitative and qualitative differences in their capacities to modulate the innate antiviral immune response in PIE cells, which would explain the higher capacity of the CRL1505 strain when compared to CRL1506 to protect against viral infection and inflammatory damage in vivo. These results provided valuable information for the deeper understanding of the host–immunobiotic interaction and their effect on antiviral immunity. The comprehensive transcriptomic analyses successfully identified a group of genes (IFN-β, RIG1, RNASEL, MX2, A20, IL27, CXCL5, CCL4, PTGES, and PTGER4), which can be used as prospective biomarkers for the screening of new antiviral immunobiotics in PIE cells and for the development of novel functional food and feeds, which may help to prevent viral infections.
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Affiliation(s)
- Leonardo Albarracin
- Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman, Argentina; Immunobiotics Research Group, Tucuman, Argentina; Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
| | - Hisakazu Kobayashi
- Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
| | - Hikaru Iida
- Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
| | - Nana Sato
- Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
| | - Tomonori Nochi
- Cell Biology Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; Infection Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
| | - Hisashi Aso
- Cell Biology Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; Infection Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
| | - Susana Salva
- Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman, Argentina; Immunobiotics Research Group, Tucuman, Argentina
| | - Susana Alvarez
- Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman, Argentina; Immunobiotics Research Group, Tucuman, Argentina
| | - Haruki Kitazawa
- Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
| | - Julio Villena
- Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman, Argentina; Immunobiotics Research Group, Tucuman, Argentina; Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
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14
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Abstract
"Rotaviruses represent the most important etiological agents of acute, severe gastroenteritis in the young of many animal species, including humans." This statement, variations of which are a common beginning in articles about rotaviruses, reflects the fact that these viruses have evolved efficient strategies for evading the innate immune response of the host and for successfully replicating in the population. In this review, we summarize what is known about the defense mechanisms that host cells employ to prevent rotavirus invasion and the countermeasures that these viruses have successfully developed to surpass cellular defenses. Rotaviruses use at least two viral multifunctional proteins to directly interact with, and prevent the activation of, the interferon system, and they use at least one other protein to halt the protein synthesis machinery and prevent the expression of most of the transcriptional antiviral program of the cell. Characterization of the confrontation between rotaviruses and their host cells has allowed us to learn about the virus-host coevolution that prevents the damaging effects of the innate immune response.
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Affiliation(s)
- Susana López
- Departamento de Génetica del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México;
| | - Liliana Sánchez-Tacuba
- Departamento de Génetica del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México;
| | - Joaquin Moreno
- Departamento de Génetica del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México;
| | - Carlos F Arias
- Departamento de Génetica del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México;
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