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

Umesh Katpally, Christiane E. Wobus, Kelly Dryden, Herbert W. Virgin IV, Thomas Smith

Research output: Contribution to journalArticle

62 Citations (Scopus)

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 ∼16Å and rotated ∼40° 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.

Original languageEnglish (US)
Pages (from-to)2079-2088
Number of pages10
JournalJournal of Virology
Volume82
Issue number5
DOIs
StatePublished - Mar 2008
Externally publishedYes

Fingerprint

Norovirus
antibodies
Antibodies
mice
virion
neutralization
Virion
Caliciviridae
Immunoglobulin Fab Fragments
Vesivirus
Cryoelectron Microscopy
Plant Viruses
capsid
Capsid
plant viruses
gastroenteritis
Gastroenteritis
Capsid Proteins
Neutralizing Antibodies
coat proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Structure of antibody-neutralized murine norovirus and unexpected differences from viruslike particles. / Katpally, Umesh; Wobus, Christiane E.; Dryden, Kelly; Virgin IV, Herbert W.; Smith, Thomas.

In: Journal of Virology, Vol. 82, No. 5, 03.2008, p. 2079-2088.

Research output: Contribution to journalArticle

Katpally, Umesh ; Wobus, Christiane E. ; Dryden, Kelly ; Virgin IV, Herbert W. ; Smith, Thomas. / Structure of antibody-neutralized murine norovirus and unexpected differences from viruslike particles. In: Journal of Virology. 2008 ; Vol. 82, No. 5. pp. 2079-2088.
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