title: Norovirus antagonism of B-cell antigen presentation results in impaired control of acute infection.
abstract: Human noroviruses are a leading cause of gastroenteritis, and so, vaccine development is desperately needed. Elucidating viral mechanisms of immune antagonism can provide key insight into designing effective immunization platforms. We recently revealed that B cells are targets of norovirus infection. Because noroviruses can regulate antigen presentation by infected macrophages and B cells can function as antigen-presenting cells, we tested whether noroviruses regulate B-cell-mediated antigen presentation and the biological consequence of such regulation. Indeed, murine noroviruses could prevent B-cell expression of antigen presentation molecules and this directly correlated with impaired control of acute infection. In addition to B cells, acute control required MHC class I molecules, CD8+T cells, and granzymes, supporting a model whereby B cells act as antigen presenting cells to activate cytotoxic CD8+T cells. This immune pathway was active prior to the induction of antiviral antibody responses. As in macrophages, the minor structural protein VP2 regulated B-cell antigen presentation in a virus-specific manner. Commensal bacteria were not required for the activation of this pathway and ultimately only B cells were required for the clearance of viral infection. These findings provide new insight into the role of B cells in stimulating antiviral CD8+T-cell responses.
authors.affiliation: College of Medicine, Department of Molecular Genetics & Microbiology, Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA.
authors.forename: S
authors.initials: S
authors.lastname: Zhu
authors.affiliation: College of Medicine, Department of Molecular Genetics & Microbiology, Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Jones
authors.affiliation: College of Medicine, Department of Molecular Genetics & Microbiology, Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA.
authors.forename: D
authors.initials: D
authors.lastname: Hickman
authors.affiliation: College of Medicine, Department of Medicine, Division of Rheumatology & Clinical Immunology, University of Florida, Gainesville, Florida, USA.
authors.forename: S
authors.initials: S
authors.lastname: Han
authors.affiliation: College of Medicine, Department of Medicine, Division of Rheumatology & Clinical Immunology, University of Florida, Gainesville, Florida, USA.
authors.forename: W
authors.initials: W
authors.lastname: Reeves
authors.affiliation: College of Medicine, Department of Molecular Genetics & Microbiology, Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Karst
mesh_terms: D000208:Acute Disease; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D017250:Caliciviridae Infections / Q000276:immunology* / Q000821:virology*; D036022:Capsid Proteins / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D004195:Disease Models, Animal; D000069196:Gastrointestinal Microbiome; D006801:Humans; D056747:Immunomodulation; D051379:Mice; D018345:Mice, Knockout; D029322:Norovirus / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D000954:Antigens, Surface; D036022:Capsid Proteins