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

Don B. Gammon, Sophie Duraffour, Daniel K. Rozelle, Heidi Hehnly, Rita Sharma, Michael E. Sparks, Cara C. West, Ying Chen, James J. Moresco, Graciela Andrei, John H. Connor, Darryl Conte, Dawn E. Gundersen-Rindal, William L. Marshall, John R. Yates, Neal Silverman, Craig C. Mello

Research output: Contribution to journalArticle

6 Scopus citations

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 ubiquitindependent targeting of viral proteins for destruction. Importantly, our studies reveal exciting new opportunities to study virus-host interactions in experimentally-tractable Lepidopteran systems.

Original languageEnglish (US)
Article number02190
JournaleLife
Volume2014
Issue number3
DOIs
StatePublished - Jun 25 2014
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Gammon, D. B., Duraffour, S., Rozelle, D. K., Hehnly, H., Sharma, R., Sparks, M. E., West, C. C., Chen, Y., Moresco, J. J., Andrei, G., Connor, J. H., Conte, D., Gundersen-Rindal, D. E., Marshall, W. L., Yates, J. R., Silverman, N., & Mello, C. C. (2014). A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection. eLife, 2014(3), [02190]. https://doi.org/10.7554/eLife.02910.001