Title: A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection
Authors: 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 C
Conte, Darryl
Gundersen-Rindal, Dawn E
Marshall, William L
Yates, John
Silverman, Neal
Mello, Craig C #
Issue Date: Aug-2014
Series Title: eLife vol:3 pages:e02910
Article number: 10.7554/eLife.02910
Abstract: 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-κB, 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.
ISSN: 2050-084X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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