Transcriptional Activation by the Product of Open Reading Frame 50 of Kaposi’s Sarcoma-Associated Herpesvirus Is Required for Lytic Viral Reactivation in B Cells

摘要: Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) is a lymphotropic virus strongly linked to the development of KS, an endothelial cell neoplasm frequent in persons with AIDS. Reactivation from latency B cells thought be important antecedent viral spread during KS pathogenesis. Earlier experiments have posited role for transcriptional activator encoded by KSHV open reading frame 50 (ORF50) such reactivation, since ectopic overexpression this protein induces reactivation latently infected cells. Here we explored several aspects expression, structure, and function bearing on role. The ORF50 gene expressed very early lytic before other genes implicated as candidate regulatory related viruses, its expression can upregulate their promoters transient assays. extensively phosphorylated vivo bears numerous sites phosphorylation kinase C, activators which are potent stimulators induction. C terminus contains domain that activate transcription when targeted DNA; deletion generates allele expresses truncated retains ability form multimers full-length functions dominant-negative protein. Expression ablates spontaneous strikingly suppresses replication induced multiple stimuli, including phorbol ester, ionomycin, sodium butyrate. These results indicate product plays essential consistent action putative molecular switch controlling induction latency.