title: Cellular and humoral immunity following Snow Mountain virus challenge.
abstract: Little is known about the immune response to noroviruses. To elucidate the immunobiology of norovirus infection in humans, 15 volunteers were challenged with Snow Mountain virus (SMV), a genogroup 2 norovirus. We assessed the cellular and humoral immune response and infection by analyzing stool, serum, saliva, and peripheral blood mononuclear cell (PBMC) responses pre- and postchallenge. In contrast to Norwalk virus (NV), SMV infection was not dependent upon blood group secretor status. Nine of 15 volunteers were infected and showed a >/=4-fold increase over the prechallenge anti-SMV serum immunoglobulin G (IgG) titer, mostly subclass IgG1. Although serum IgG elicited by SMV infection was cross-reactive with Hawaii virus (HV), another genogroup 2 norovirus, salivary IgA was less cross-reactive. Neither SMV-elicited serum IgG nor salivary IgA cross-reacted with NV, a genogroup 1 norovirus. Significant increases in serum gamma interferon (IFN-gamma) and IL-2, but not IL-6 or IL-10, were noted on day 2 postchallenge. For the majority of volunteers, both infected and uninfected, PBMCs stimulated with norovirus virus-like particles secreted IFN-gamma and other Th1 cytokines, suggesting previous norovirus exposure in most volunteers. Like the IgG antibodies, the SMV-activated T cells were cross-reactive with HV but not NV. IFN-gamma production was dependent upon CD4(+) cells, consistent with a predominant, but not exclusive, Th1 response. To our knowledge, this is the first report characterizing T-cell and cytokine responses following live norovirus challenge.
authors.affiliation: School of Public Health, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Lindesmith
authors.forename: Christine
authors.initials: C
authors.lastname: Moe
authors.forename: Jacques
authors.initials: J
authors.lastname: Lependu
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Frelinger
authors.forename: John
authors.initials: J
authors.lastname: Treanor
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Baric
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood; D000956:Antigens, Viral / Q000008:administration & dosage / Q000302:isolation & purification; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D017250:Caliciviridae Infections / Q000276:immunology* / Q000821:virology; D003429:Cross Reactions; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005759:Gastroenteritis / Q000276:immunology* / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000097:blood; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D029322:Norovirus / Q000276:immunology* / Q000472:pathogenicity*; D012463:Saliva / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D016207:Cytokines; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G