Distant homolog identifies novel viral immune evasins from herpesvirus proteome (VIR5P.1031)

Abstract

Abstract Viruses have evolved a number of mechanisms to avoid host immune responses. Herpesviruses have been known as a rich source in viral evasion genes including homologs mimicking the structures and functions of host immune proteins. Using a rapid high throughput computational structural mimicry analysis, we have screening the whole proteome of human herpesviruses that includes nearly 2,000 proteins. We discovered a number of novel distant viral homologs in herpesvirus proteome that are previously uncharacterized. This includes homologs involving MHC class I pathways and NK immune defense, or chemokine and cytokine mimics. Sequence identities between viral mimics and native host ligands/receptors can be as low as 9-25%. Two novel distant homologs are of particular interests as they are predicted to be involved in MHC class I modulation. These novel homologs are being expressed and produced and are undergone further characterization to determine their structural and functional characteristics and their roles in viral immune evasion. From these herpesviral homologs and their predicted structures, we hypothesize that herpesviruses utilize a variety of binding mechanisms to regulate a class of key MHC I molecules including MICA/B.