Regulation of norovirus virulence by the VP1 protruding domain correlates with B cell infection efficiency

Shu Zhu, Makiko Watanabe, Ericka Kirkpatrick, Akilah B. Murray, Ryneth Sok, Stephanie M. Karst

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Human noroviruses are a leading cause of gastroenteritis across the globe, but the pathogenic mechanisms responsible for disease are not well established. The availability of a murine norovirus model system provides the opportunity to elucidate viral and host determinants of virulence in a natural host. For example, previous studies have revealed that the protruding domain of the murine norovirus capsid protein VP1, specifically residue 296 of VP1, regulates virulent infection. We identified a panel of nonsynonymous mutations in the open reading frame 2 (ORF2) gene encoding VP1 that arose in persistently infected mice and tested whether these mutations conferred phenotypic changes to viral replication and virulence. Consistent with previous studies, we demonstrate that a glutamic acid at position 296 results in attenuation. For the first time, we also demonstrate that a lysine at this position is sufficient to confer virulence on an otherwise attenuated murine norovirus strain. Moreover, our studies reveal a direct correlation between the efficiency of viral replication in B cells and virulence. These data are especially striking because mutations causing reduced B cell replication and attenuation had minimal effects on the ability of the virus to replicate in macrophages. Thus, norovirus infection of B cells may directly contribute to disease outcome.

Original languageEnglish
Pages (from-to)2858-2867
Number of pages10
JournalJournal of Virology
Volume90
Issue number6
DOIs
StatePublished - 2016
Externally publishedYes

Fingerprint

Dive into the research topics of 'Regulation of norovirus virulence by the VP1 protruding domain correlates with B cell infection efficiency'. Together they form a unique fingerprint.

Cite this