|GAMMON, DON - University Of Massachusetts|
|DURAFFOUR, SOPHIE - Leuven University|
|HEHNLY, HEIDI - University Of Massachusetts|
|ROZELLE, DAN - Boston University|
|SHARMA, RITA - University Of Massachusetts|
|WEST, CARA - University Of Massachusetts|
|ANDREI, GRACIELA - Leuven University|
|CONNOR, JOHN - Boston University|
|CONTE, JOHN - University Of Massachusetts|
|DOXSEY, STEPHEN - University Of Massachusetts|
|MARSHALL, WILLIAM - Merck Research Laboratories|
|SILVERMAN, NEIL - University Of Massachusetts|
|MELLO, CRAIG - University Of Massachusetts|
Submitted to: Cell Host and Microbe
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/25/2014
Publication Date: 6/25/2014
Citation: Gammon, D.B., Duraffour, S., Hehnly, H., Rozelle, D.K., Sharma, R., Sparks, M., West, C.C., Andrei, G., Connor, J.H., Conte, J., Doxsey, S., Gundersen, D.E., Marshall, W.L., Silverman, N., Mello, C.C. 2014. A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection. Cell Host and Microbe. eLife 25:3. doi: 10.7554/eLife.02910.
Interpretive Summary: The interactions of viruses with hosts result in development of a diversity of immune responses and anti-virus countermeasures. Some viruses are host-limited, while others infect a broad array of hosts. There are many factors that affect the ability of viruses to enter and infect host cells. Few studies have examined infection processes of human-associated viruses in cells of insect origin. In this study we found two RNA viruses that usually infect a very broad range of hosts were restricted in or unable to infect cells of moth origin. However, the same RNA viruses were able to replicate in moth cells when they were co-infected with a human vaccinia pox DNA virus. This study examined the factors associated with the DNA virus that relieved RNA virus restriction and showed the A51R protein encoded by the DNA virus relieved the RNA virus restriction. The study also examined the functions of the gene A51R, which is important for vaccinia virus replication and pathogenesis in vertebrate hosts. This study may lead to new strategies to overcome antiviral responses of Lepidopteran/caterpillar pests and lead to more effective biocontrol agents. This information will be used by academic and industry scientists interested in novel insect biocontrol.
Technical Abstract: Virus-host interactions drive a remarkable diversity of immune responses and countermeasures. While investigating virus-invertebrate host interactions we found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), were unable to infect certain Lepidopteran cells. Interestingly, this restriction was overcome when these insect cells were co-infected with vaccinia virus (VACV), a vertebrate DNA virus. Using RNAi we identify cellular genes that mediate restriction to RNA virus infection. We also show that a highly-conserved but uncharacterized VACV gene, A51R, is sufficient to overcome RNA virus restriction. We show that A51R protein associates with microtubules in both vertebrate and insect cells. Finally, we show that A51R is critical for VACV replication in vertebrate cells and for pathogenesis in mice. Our studies shed light on the potential function of a highly conserved poxvirus gene and reveal exciting new opportunities to study virus-host interactions in experimentally-tractable Lepidopteran systems.