TY - JOUR TI - 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, Jr. AU - Gundersen-Rindal, Dawn E AU - Marshall, William L AU - Yates, John R AU - Silverman, Neal AU - Mello, Craig C A2 - Medzhitov, Ruslan VL - 3 PY - 2014 DA - 2014/06/25 SP - e02910 C1 - eLife 2014;3:e02910 DO - 10.7554/eLife.02910 UR - https://doi.org/10.7554/eLife.02910 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 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. KW - Lymantria dispar KW - vaccinia virus KW - vesicular stomatitis virus KW - Sindbis virus KW - microtubules KW - ubiquitin JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -