A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection
AuthorsGammon, Don B.
Rozelle, Daniel K.
Sparks, Michael E.
West, Cara C.
Moresco, James J.
Connor, John H.
Conte, Darryl Jr.
Gundersen-Rindal, Dawn E.
Marshall, William L.
Yates, John R.
Silverman, Neal S.
Mello, Craig C.
UMass Chan AffiliationsRNA Therapeutics Institute
Program in Molecular Medicine
Department of Medicine, Division of Infectious Diseases and Immunology
Document TypeJournal Article
Microbiology and infectious disease
vesicular stomatitis virus
Immunology and Infectious Disease
Immunology of Infectious Disease
MetadataShow full item record
AbstractVirus-host interactions drive a remarkable diversity of immune responses and countermeasures. We found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), are completely restricted in their replication after entry into Lepidopteran cells. This restriction is overcome when cells are co-infected with vaccinia virus (VACV), a vertebrate DNA virus. Using RNAi screening, we show that Lepidopteran RNAi, Nuclear Factor-kappaB, and ubiquitin-proteasome pathways restrict RNA virus infection. Surprisingly, a highly conserved, uncharacterized VACV protein, A51R, can partially overcome this virus restriction. We show that A51R is also critical for VACV replication in vertebrate cells and for pathogenesis in mice. Interestingly, A51R colocalizes with, and stabilizes, host microtubules and also associates with ubiquitin. We show that A51R promotes viral protein stability, possibly by preventing ubiquitin-dependent targeting of viral proteins for destruction. Importantly, our studies reveal exciting new opportunities to study virus-host interactions in experimentally-tractable Lepidopteran systems.
SourceElife. 2014 Jun 25;3. doi: 10.7554/eLife.02910. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/34950
Related ResourcesLink to Article in PubMed
RightsThis is an open-access article, free of all copyright, and may befreely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under theCreative Commons CC0 public domain dedication.
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