A single-amino-acid change in murine norovirus NS1/2 is sufficient for colonic tropism and persistence.
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.
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Timothy J
TJ
Nice
David W
DW
Strong
Broc T
BT
McCune
Calvin S
CS
Pohl
Herbert W
HW
Virgin
D000818:Animals; D017250:Caliciviridae Infections / Q000821:virology*; D002353:Carrier State / Q000821:virology*; D003106:Colon / Q000821:virology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D029322:Norovirus / Q000235:genetics* / Q000502:physiology*; D017354:Point Mutation; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism; D056189:Viral Tropism
D050505:Mutant Proteins; D017361:Viral Nonstructural Proteins