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.DOI: http://dx.doi.org/10.7554/eLife.02910.001

Cytokine Diedel and a viral homologue suppress the IMD pathway in Drosophila

“…27, see also refs. [43][44][45][46]. Of note, imd or IKKγ mutant flies were not more susceptible to SINV infection than wild-type controls in our conditions (SI Appendix, Fig.…”

Infection of Caenorhabditis elegans with Vesicular Stomatitis Virus via Microinjection

“…At specific intervals post-infection (typically 24-72 hpi), worms should be harvested from each treatment to score for luciferase activity, which is used as a readout for VSV-LUC replication (Gammon et al , 2014 and 2017). …”

The diversity of insect antiviral immunity: insights from viruses

“…mosquitoes, flies, bees, lepidopterans and even non-insect arthropods such as ticks) [4–12]. RNAi refers to a series of mechanisms of gene regulation mediated by small RNAs associated with proteins of the Argonaute family that drive degradation of viral RNA in a sequence specific manner [13].…”

“…In addition, several other pathways have been reported to play a role in insect antiviral defense, such as the ubiquitin proteasome pathway, autophagy or heat-shock response [12,20,26,32]. This plethora of insect strategies to counteract viruses may reflect the selective pressure these pathogens impose on a very diverse group of hosts.…”

“…Insect viruses that have been used can be divided into opportunistic or natural pathogens, both of which can cause acute or persistent infections [38]. Opportunistic or non-natural pathogens are less likely to be well adapted to the host and thus more likely to reveal antiviral mechanisms [12]. Natural viruses, on the other hand, might not activate these mechanisms because they either encode suppressors or avoid recognition.…”