Characterization of PKR Allelic Diversity in African Green Monkeys

Double stranded RNA is characteristic of viral infection, triggering an antiviral response through the activation of protein kinase R (PKR). PKR binds dsRNA causing PKR to dimerize, autophosphorylate and subsequently phosphorylate the translation initiation factor eukaryotic initiation factor 2α (eIF2α) which inhibits protein synthesis in virus infected cells. In response to the anti-viral activity of PKR, most viruses have evolved mechanisms to inhibit PKR. For example, Human Cytomegalovirus (HCMV) requires either TRS1 or IRS1 to inhibit PKR activation. Rhesus Cytomegalovirus (RhCMV) is an established animal model for HCMV, and encodes a homolog of TRS1 (RhTRS1), but not IRS1 based on genomic and sequence homology along with the ability to bind dsRNA. Interestingly, RhTRS1 has been found to inhibit PKR in African green monkey (AGM) derived cell lines but not in primary AGM fibroblasts. The AGM lineage has at least four defined species that are geographically isolated and have morphological differences. Multiple polymorphisms between the PKR gene of AGM vervet and tantalus species have been identified. One possible hypothesis is the allelic variation of PKR may correlate with species diversity in the AGM lineage. Therefore, I am sequencing the last two exons of the PKR gene from multiple different species of AGM to determine the diversity of PKR alleles in these animals. Identification of allelic variation will improve AGMs as a biological model; characterizing PKR diversity will improve the selection of appropriate animal subjects for future experimentation.