Kaposi's Sarcoma-Associated Herpesvirus-Encoded Replication and Transcription Activator Impairs Innate Immunity via Ubiquitin-Mediated Degradation of Myeloid Differentiation Factor 88

Abstract

MyD88 is an adaptor for all TLRs other than TLR3, and it mediates inflammatory factors and IFN production. Our study demonstrated that the KSHV RTA protein functions as an E3 ligase to degrade MyD88 through the ubiquitin-proteasome pathway and block the transmission of TLRs signals. Moreover, we found that KSHV inhibited MyD88 expression during the early stage of de novo infection as well as in lytic reactivation. These results provide a potential mechanism for the virus to evade innate immunity.