Protruding domain of capsid protein is necessary and sufficient to determine murine norovirus replication and pathogenesis in vivo

David W. Strong, Larissa B. Thackray, Tom J. Smith, Herbert W. Virgin

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Human noroviruses (HuNoVs) are the major cause of epidemic, nonbacterial gastroenteritis worldwide. Due to the lack of a tractable model system and the inability to grow HuNoVs in cell culture, factors required for the norovirus (NoV) life cycle and pathogenesis in the host remain largely unknown. The discovery of murine norovirus (MNV) and the development of reversegenetics systems for this virus provide an opportunity to study these aspects of NoV infection in vitro and in vivo. Previous studies identified a single amino acid at residue 296 in the protruding (P) domain of the capsid protein that is responsible for determining the virulence of the MNV clone MNV1.CW1 in 12956/SvEv background STAT1-deficient (STAT1 -/ -) mice. In this report, we identified and characterized another determinant of lethality in the P domain that is necessary and sufficient to determine the replication and pathogenesis of the MNV clones MNV1.CW3 and CR6.STL1 in C57BL/6 background STAT1 -/ - mice. Furthermore, we describe how the role of residue 296 in MNV virulence differs between STAT1 -/ - mouse strains. We also describe potential interactions between subdomains of the P domain, as well as between other virus elements, which facilitate recovery of MNV using a reverse-genetics system.

Original languageEnglish (US)
Pages (from-to)2950-2958
Number of pages9
JournalJournal of virology
Volume86
Issue number6
DOIs
StatePublished - Mar 1 2012
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this