A single-amino-acid change in murine norovirus NS1/2 is sufficient for colonic tropism and persistence

Timothy Nice, David W. Strong, Broc T. McCune, Calvin S. Pohl, Herbert W. Virgin

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Human norovirus (HuNoV) is the major cause of acute nonbacterial gastroenteritis worldwide but has no clear animal reservoir. HuNoV can persist after the resolution of symptoms, and this persistence may be essential for viral maintenance within the population. Many strains of the related murine norovirus (MNV) also persist, providing a tractable animal model for studying norovirus (NoV) persistence. We have used recombinant cDNA clones of representative persistent (CR6) and nonpersistent (CW3) strains to identify a domain within the nonstructural gene NS1/2 that is necessary and sufficient for persistence. Furthermore, we found that a single change of aspartic acid to glutamic acid in CW3 NS1/2 was sufficient for persistence. This same conservative change also caused increased growth of CW3 in the proximal colon, which we found to be a major tissue reservoir of MNV persistence, suggesting that NS1/2 determines viral tropism that is necessary for persistence. These findings represent the first identified function for NoV NS1/2 during infection and establish a novel model system for the study of enteric viral persistence.

Original languageEnglish (US)
Pages (from-to)327-334
Number of pages8
JournalJournal of Virology
Volume87
Issue number1
DOIs
StatePublished - Jan 2013
Externally publishedYes

Fingerprint

Norovirus
tropisms
Tropism
Amino Acids
amino acids
mice
Viral Tropism
gastroenteritis
Gastroenteritis
aspartic acid
glutamic acid
Aspartic Acid
signs and symptoms (animals and humans)
colon
Glutamic Acid
Colon
Animal Models
Complementary DNA
Clone Cells
animal models

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

A single-amino-acid change in murine norovirus NS1/2 is sufficient for colonic tropism and persistence. / Nice, Timothy; Strong, David W.; McCune, Broc T.; Pohl, Calvin S.; Virgin, Herbert W.

In: Journal of Virology, Vol. 87, No. 1, 01.2013, p. 327-334.

Research output: Contribution to journalArticle

Nice, Timothy ; Strong, David W. ; McCune, Broc T. ; Pohl, Calvin S. ; Virgin, Herbert W. / A single-amino-acid change in murine norovirus NS1/2 is sufficient for colonic tropism and persistence. In: Journal of Virology. 2013 ; Vol. 87, No. 1. pp. 327-334.
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