Intrinsic immune responses are the cell’s first line of defense against invading pathogens. In virus-infected cells these responses are activated following detection of pathogen-associated molecular patterns (PAMPs) that are normally absent from uninfected cells (e.g. viral genomic RNA).
One of the activated responses is the transient translation arrest. This arrest interferes with viral gene expression because viruses are dependent on host translation machinery for their own protein synthesis. Following translation arrest, polysome-free messenger ribonucleoproteins recruit RNA-binding proteins with self-aggregating properties which nucleate the formation of stress granules (SGs) in the cytoplasm of virus-infected cells.
Many viruses evolved countermeasures that prevent translation arrest and SG formation. Interestingly, SG inhibition is often blocked by viruses even when global translation arrest is induced, suggesting that in addition to being the indicators of global translation arrest, SGs themselves may have antiviral functions. Characterizing the functional role of SG formation in innate immune responses is one of our research objectives.
McCormick, C. and Khaperskyy, D.A. (2017) Translation inhibition and stress granules in the antiviral immune response. Nat. Rev. Immunol. 10:647-660.
Khaperskyy, D.A., Emara, M. M., Johnston, B.P., Anderson, P., Hatchette, T.F., and McCormick, C. (2014) Influenza A virus host shutoff disables antiviral stress-induced translation arrest. PLoS Pathog. 10: e1004217.
Khaperskyy, D.A., Hatchette, T.F., and McCormick, C. (2012) Influenza A virus inhibits cytoplasmic stress granule formation. FASEB J. 26: 1629-39.