Stress granules are RNA-protein complexes that assemble in response to an external stress cue, such as a viral infection. These RNA-protein granules function to protect the integrity of cellular mRNAs by repressing translation, sorting and storing mRNAs, aggregating critical antiviral factors and thus amplifying the innate immune response, and sequestering pro-apoptotic proteins to protect cells from cell death signaling pathways. As such, stress granules present a particularly perilous environment for viruses, particularly those that replicate in the cytoplasm. Indeed, many viruses directly subvert distinct stress granule components to inhibit their formation or integrity, and to promote distinct steps in the viral life cycle.
We have shown that Zika virus disrupts the formation of stress granules by relocalizing specific RNA-binding proteins to viral replication complexes. Moreover, we determined that select stress granule proteins are critical for Zika virus gene expression, while other RNA-binding proteins function to limit viral replication. Using molecular and cell biological approaches, and next generation sequence analysis our goal is to investigate the molecular consequences of ZIKV-infection on the formation of stress granules and stability of cellular mRNAs, two RNA metabolism pathways that, if misregulated, could contribute to the neuropathogenesis and developmental malformations linked with congenital Zika virus infections.