title: Newly isolated mAbs broaden the neutralizing epitope in murine norovirus.
abstract: Here, we report the isolation and functional characterization of mAbs against two murine norovirus (MNV) strains, MNV-1 and WU20, which were isolated following oral infection of mice. The mAbs were screened for reactivity against the respective homologous and heterologous MNV strain by ELISA. Selected mAbs were of IgA, IgG1, IgG2a or IgG2b isotype and showed a range of Western blot reactivities from non-binding to strong binding, suggesting recognition of conformational and linear epitopes. Some of the anti-MNV-1 antibodies neutralized both MNV-1 and WU20 infections in culture and in mice, but none of the anti-WU20 mAbs neutralized either virus. The non-neutralizing anti-MNV-1 IgG2b antibody 5C4.10 was mapped to the S domain of the MNV-1 capsid, whilst the epitopes of the neutralizing anti-MNV-1 IgA antibodies 2D3.7 and 4F9.4 were mapped to the P domain. Generation of neutralization escape viruses showed that two mutations (V339I and D348E) in the C'D' loop of the MNV-1 P domain mediated escape from mAb 2D3.7 and 4F9.4 neutralization. These findings broaden the known neutralizing epitopes of MNV to the main surface-exposed loops of the P domain. In addition, the current panel of antibodies provides valuable reagents for studying norovirus biology and development of diagnostic tools.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Abimbola O
authors.initials: AO
authors.lastname: Kolawole
authors.affiliation: Donald Danforth Plant Science Center, St Louis, MO, USA.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Xia
authors.affiliation: Donald Danforth Plant Science Center, St Louis, MO, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Gamez
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Rippinger
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Yucha
authors.affiliation: Donald Danforth Plant Science Center, St Louis, MO, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Smith
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Christiane E
authors.initials: CE
authors.lastname: Wobus
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000235:genetics / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000918:Antibody Specificity; D017250:Caliciviridae Infections / Q000276:immunology; D002213:Capsid / Q000276:immunology; D036022:Capsid Proteins / Q000276:immunology*; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008264:Macrophages; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D029322:Norovirus / Q000235:genetics / Q000276:immunology*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D019562:Viral Load
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D000939:Epitopes; D007070:Immunoglobulin A; D007074:Immunoglobulin G