Structure of antibody-neutralized murine norovirus and unexpected differences from viruslike particles

J Virol. 2008 Mar;82(5):2079-88. doi: 10.1128/JVI.02200-07. Epub 2007 Dec 19.

Abstract

Noroviruses (family Caliciviridae) are the major cause of epidemic nonbacterial gastroenteritis in humans, but the mechanism of antibody neutralization is unknown and no structure of an infectious virion has been reported. Murine norovirus (MNV) is the only norovirus that can be grown in tissue culture, studied in an animal model, and reverse engineered via an infectious clone and to which neutralizing antibodies have been isolated. Presented here are the cryoelectron microscopy structures of an MNV virion and the virion in complex with neutralizing Fab fragments. The most striking differences between MNV and previous calicivirus structures are that the protruding domain is lifted off the shell domain by approximately 16A and rotated approximately 40 degrees in a clockwise fashion and forms new interactions at the P1 base that create a cagelike structure engulfing the shell domains. Neutralizing Fab fragments cover the outer surface of each copy of the capsid protein P2 domains without causing any apparent conformational changes. These unique features of MNV suggest that at least some caliciviruses undergo a capsid maturation process akin to that observed with other plant and bacterial viruses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Viral / immunology*
  • Cell Line
  • Cryoelectron Microscopy
  • Immunoglobulin Fab Fragments / immunology
  • Mice
  • Molecular Sequence Data
  • Neutralization Tests
  • Norovirus / immunology*
  • Norovirus / ultrastructure
  • Sequence Homology, Amino Acid
  • Virion / ultrastructure*

Substances

  • Antibodies, Viral
  • Immunoglobulin Fab Fragments