TY - JOUR
T1 - A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection
AU - Gammon, Don B.
AU - Duraffour, Sophie
AU - Rozelle, Daniel K.
AU - Hehnly, Heidi
AU - Sharma, Rita
AU - Sparks, Michael E.
AU - West, Cara C.
AU - Chen, Ying
AU - Moresco, James J.
AU - Andrei, Graciela
AU - Connor, John H.
AU - Conte, Darryl
AU - Gundersen-Rindal, Dawn E.
AU - Marshall, William L.
AU - Yates, John R.
AU - Silverman, Neal
AU - Mello, Craig C.
PY - 2014/6/25
Y1 - 2014/6/25
N2 - 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 ubiquitindependent targeting of viral proteins for destruction. Importantly, our studies reveal exciting new opportunities to study virus-host interactions in experimentally-tractable Lepidopteran systems.
AB - 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 ubiquitindependent 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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UR - http://www.scopus.com/inward/citedby.url?scp=84905167806&partnerID=8YFLogxK
U2 - 10.7554/eLife.02910.001
DO - 10.7554/eLife.02910.001
M3 - Article
C2 - 24966209
AN - SCOPUS:84905167806
SN - 2050-084X
VL - 2014
JO - eLife
JF - eLife
IS - 3
M1 - 02190
ER -