title: A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection.
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.
authors: RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, United States.
authors: Don B
authors: DB
authors: Gammon
authors: Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors: Sophie
authors: S
authors: Duraffour
authors: Department of Microbiology, Boston University, Boston, United States.
authors: Daniel K
authors: DK
authors: Rozelle
authors: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States.
authors: Heidi
authors: H
authors: Hehnly
authors: RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, United States.
authors: Rita
authors: R
authors: Sharma
authors: Agricultural Research Service, United States Department of Agriculture, Beltsville, United States.
authors: Michael E
authors: ME
authors: Sparks
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, United States.
authors: Cara C
authors: CC
authors: West
authors: RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, United States.
authors: Ying
authors: Y
authors: Chen
authors: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, United States.
authors: James J
authors: JJ
authors: Moresco
authors: Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors: Graciela
authors: G
authors: Andrei
authors: Department of Microbiology, Boston University, Boston, United States.
authors: John H
authors: JH
authors: Connor
authors: RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, United States.
authors: Darryl
authors: D
authors: Conte
authors: Agricultural Research Service, United States Department of Agriculture, Beltsville, United States.
authors: Dawn E
authors: DE
authors: Gundersen-Rindal
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, United States.
authors: William L
authors: WL
authors: Marshall
authors: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, United States.
authors: John R
authors: JR
authors: Yates
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, United States.
authors: Neal
authors: N
authors: Silverman
authors: RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, United States.
authors: Craig C
authors: CC
authors: Mello
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004279:DNA, Viral / Q000737:chemistry; D006801:Humans; D007915:Lepidoptera / Q000276:immunology / Q000821:virology*; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry; D034622:RNA Interference; D025801:Ubiquitin / Q000737:chemistry; D014616:Vaccinia virus / Q000502:physiology*; D018116:Vesiculovirus / Q000502:physiology*; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D025801:Ubiquitin; D014764:Viral Proteins; D046988:Proteasome Endopeptidase Complex
keywords: Lymantria dispar; Sindbis virus; immunology; infectious disease; microbiology; microtubules; mouse; ubiquitin; vaccinia virus; vesicular stomatitis virus; viruses