Department of Medicine, Division of Infectious Diseases and Immunology; Program in Molecular Medicine; RNA Therapeutics Institute
Virus-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.
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Citation: Elife. 2014 Jun 25;3. doi: 10.7554/eLife.02910. Link to article on publisher's site
Immunology, Microbiology and infectious disease, Lymantria dispar, vaccinia virus, vesicular stomatitis virus, Sindbis virus, microtubules, ubiquitin, Mouse Viruses
Gammon, Don B.; Duraffour, Sophie; Rozelle, Daniel K.; Hehnly, Heidi; Sharma, Rita; Sparks, Michael E.; West, Cara C.; Chen, Ying; Moresco, James J.; Andrei, Graciela; Connor, John H.; Conte, Darryl Jr.; Gundersen-Rindal, Dawn E.; Marshall, William L.; Yates, John R.; Silverman, Neal S.; and Mello, Craig C., "A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection" (2014). Infectious Diseases and Immunology Publications and Presentations. 172.