Kaposi Sarcoma-associated herpesvirus (KSHV, HHV-8) is a human oncovirus with a two-stage life cycle consisting of latent and lytic replication. Lytic replication is characterized by the expression of late genes, the assembly of viral particles, and is initiated by the expression of RTA. In addition to being a transcription factor, RTA is an E3 ubiquitin ligase with the ability to target proteins for degradation via the ubiquitin-proteasome system (UPS). Previously in our lab, through a comparative proteomics study, we identified proteins that displayed increased ubiquitination in the presence of RTA. Three proteins identified are known to be involved in the process of antigen presentation. We hypothesize KSHV RTA is targeting these proteins to maintain a persistent infection. Here we provide preliminary evidence that suggests that RTA targets the process of antigen processing and presentation. suggesting a novel mechanism for evasion of the immune response by KSHV RTA. We demonstrate degradation of HLA, PSMB3, and TAP2 cells expressing RTA. Cells expressing RTA exhibited decreased peptide loading on HLA. Our data suggests a novel mechanism for evasion of the host immune response by KSHV RTA.
This project was funded through NIH 1 R15 GM118011-01 and 1F33GM130382-01 awarded to Dr. Ehrlich and The Bridges to the Doctorate Program NIH R25GM119970
