RESEARCH ARTICLE elifesciences.org A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection Don B Gammon1, Sophie Duraffour2, Daniel K Rozelle3, Heidi Hehnly4, Rita Sharma1,5, Michael E Sparks6†, Cara C West7, Ying Chen1, James J Moresco8, Graciela Andrei2, John H Connor3, Darryl Conte Jr.1, Dawn E Gundersen-Rindal6, William L Marshall7‡, John R Yates8, Neal Silverman7, Craig C Mello1,5* 1RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, United States; 2Rega Institute for Medical Research, KU Leuven, Leuven, Belgium; 3Department of Microbiology, Boston University, Boston, United States; 4Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States; 5Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, United States; 6Agricultural Research Service, United States Department of Agriculture, Beltsville, United States; 7Department of Medicine, University of Massachusetts Medical School, Worcester, United States; 8Department of Chemical Physiology, The Scripps Research Institute, La Jolla, United States *For correspondence: craig.
[email protected] Abstract Virus-host interactions drive a remarkable diversity of immune responses and Present address: †Multidrug- countermeasures. We found that two RNA viruses with broad host ranges, vesicular stomatitis resistant Organism Repository virus (VSV) and Sindbis virus (SINV), are completely restricted in their replication after entry into and Surveillance Network, Walter Lepidopteran cells. This restriction is overcome when cells are co-infected with vaccinia virus Reed Army Institute of Research, (VACV), a vertebrate DNA virus. Using RNAi screening, we show that Lepidopteran RNAi, Nuclear Silver Spring, United States; Factor-κB, and ubiquitin-proteasome pathways restrict RNA virus infection. Surprisingly, a highly ‡Merck Research Laboratories, conserved, uncharacterized VACV protein, A51R, can partially overcome this virus restriction.