Host cell substrates of RNA virus proteases

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Dicistroviruses are RNA viruses that mainly infect arthropods and have had a negative impact of agriculture and economic importance. Members include the honeybee viruses that have been associated with honeybee disease and the Taura syndrome virus, which has led to disease outbreaks in the panaeid shrimp industry. To date, the life cycle and virus host interactions are not fully understood and thus, has impacted our understanding of these viruses and limited potential antiviral strategies. However, infection of Drosophila (fruit fly) by the model dicistrovirus cricket paralysis virus (CrPV) has been instrumental in deciphering key processes into how dicistroviruses commandeer the host cell. One of the signature properties of dicistroviruses is that the virus expresses a protein, called a protease, which cleaves host proteins in the cell to facilitate virus infection. Currently, the extent of host proteins targeted by the viral protease is not known. In this study, we will utilize a novel unbiased proteomics approach called TAILS to comprehensively identify all of the targets of the dicistrovirus CrPV protease in Drosophila cells. Unlike other methods, this new TAILS approach is sensitive and can identify the location of the cleavage site on the target protein. The identification of novel targets will provide a catalog of the host processes that are affected during dicistrovirus infection. Importantly, the knowledge gained will allow us to identify new targets for antiviral therapy. The development of this strategy can be exploited to identify the repertoire of host targets of proteases from other viruses, ultimately leading to better treatment protocols for a range of virus infections causing pathological disease.