title: Adaptive immunity restricts replication of novel murine astroviruses.
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 infecting research 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 small-animal 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.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Christine C
authors.initials: CC
authors.lastname: Yokoyama
authors.forename: Joy
authors.initials: J
authors.lastname: Loh
authors.forename: Guoyan
authors.initials: G
authors.lastname: Zhao
authors.forename: Thaddeus S
authors.initials: TS
authors.lastname: Stappenbeck
authors.forename: David
authors.initials: D
authors.lastname: Wang
authors.forename: Henry V
authors.initials: HV
authors.lastname: Huang
authors.forename: Herbert W
authors.initials: HW
authors.lastname: Virgin
authors.forename: Larissa B
authors.initials: LB
authors.lastname: Thackray
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D019350:Astroviridae Infections / Q000378:metabolism* / Q000821:virology*; D004195:Disease Models, Animal; D005260:Female; D016679:Genome, Viral; D018398:Homeodomain Proteins / Q000235:genetics; D001257:Mamastrovirus / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010802:Phylogeny; D050794:STAT1 Transcription Factor / Q000235:genetics; D017422:Sequence Analysis, DNA; D012984:Software
chemical_list: D018398:Homeodomain Proteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; C064658:RAG-1 protein