Adaptive immunity restricts replication of novel murine astroviruses

Christine C. Yokoyama, Joy Loh, Guoyan Zhao, Thaddeus S. Stappenbeck, David Wang, Henry V. Huang, Herbert W. Virgin, Larissa B. Thackray

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

The mechanisms of astrovirus pathogenesis are largely unknown, in part due to a lack of a small-animal model of disease. Using shotgun sequencing and a custom analysis pipeline, we identified two novel astroviruses capable of infectingresearch mice, murine astrovirus (MuAstV) STL1 and STL2. Subsequent analysis revealed the presence of at least two additional viruses (MuAstV STL3 and STL4), suggestive of a diverse population of murine astroviruses in research mice. Complete genomic characterization and subsequent phylogenetic analysis showed that MuAstV STL1 to STL4 are members of the mamastrovirus genus and are likely members of a new mamastrovirus genogroup. Using Rag1-/- mice deficient in B and T cells, we demonstrate that adaptive immunity is required to control MuAstV infection. Furthermore, using Stat1-/- mice deficient in innate signaling, we demonstrate a role for the innate immune response in the control of MuAstV replication. Our results demonstrate that MuAstV STL permits the study of the mechanisms of astrovirus infection and host-pathogen interactions in a genetically manipulable smallanimal model. Finally, we detected MuAstV in commercially available mice, suggesting that these viruses may be present in academic and commercial research mouse facilities, with possible implications for interpretation of data generated in current mouse models of disease.

Original languageEnglish
Pages (from-to)12262-12270
Number of pages9
JournalJournal of virology
Volume86
Issue number22
DOIs
StatePublished - Nov 2012

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