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Elife. 2014 Jun 25;3. doi: 10.7554/eLife.02910.

A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection.

Author information

1
RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, United States.
2
Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
3
Department of Microbiology, Boston University, Boston, United States.
4
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States.
5
Agricultural Research Service, United States Department of Agriculture, Beltsville, United States.
6
Department of Medicine, University of Massachusetts Medical School, Worcester, United States.
7
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, United States.

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.

KEYWORDS:

Lymantria dispar; Sindbis virus; immunology; infectious disease; microbiology; microtubules; mouse; ubiquitin; vaccinia virus; vesicular stomatitis virus; viruses

PMID:
24966209
PMCID:
PMC4112549
DOI:
10.7554/eLife.02910
[Indexed for MEDLINE]
Free PMC Article
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