A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection
- University of Massachusetts Medical School, United States
- KU Leuven, Belgium
- Boston University, United States
- Walter Reed Army Institute of Research, United States
- The Scripps Research Institute, United States
- United States Department of Agriculture, United States
- Merck, 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.
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Ethics
Animal experimentation: All animal work was approved by the Katholieke Universiteit Leuven Ethics Committee for Animal Care and Use (Permit number: P044-2010) and all animal guidelines and policies were in accordance with the Belgian Royal Decree of 14 November 1993 and the European Directive 86-609-EEC.When necessary, animals were euthanized by administering pentobarbital sodium.
Reviewing Editor
- Ruslan Medzhitov, Yale University School of Medicine, United States
Publication history
- Received: March 26, 2014
- Accepted: June 25, 2014
- Accepted Manuscript published: June 25, 2014 (version 1)
- Accepted Manuscript updated: June 26, 2014 (version 2)
- Version of Record published: July 29, 2014 (version 3)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection
eLife 3:e02910.
https://doi.org/10.7554/eLife.02910
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