A Single Amino Acid Dictates Protein Kinase R Susceptibility to Unrelated Viral Antagonists.

ABSTRACT: During millions of years of coevolution with their hosts, cytomegaloviruses (CMVs) have succeeded in adapting to overcome host-specific immune defenses, including the protein kinase R (PKR) pathway. Consequently, these adaptations may also contribute to the inability of CMVs to cross species barriers. Here, we provide evidence that the evolutionary arms race between the antiviral factor PKR and its CMV antagonist TRS1 has led to extensive differences in the species-specificity of primate CMV TRS1 proteins. Moreover, we identify a single residue in human PKR that when mutated to the amino acid present in African green monkey (Agm) PKR (F489S) is sufficient to confer resistance to HCMVTRS1. Notably, this precise molecular determinant of PKR resistance has evolved under strong positive select

SUBMITTER: Carpentier KS 

PROVIDER: S-EPMC5079575 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature