Hsp70 Isoforms Are Essential for the Formation of Kaposi's Sarcoma-Associated Herpesvirus Replication and Transcription Compartments.

摘要: Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic associated with various AIDS-related malignancies. Like other herpesviruses, multiple processes required for KSHV lytic replication, including viral transcription, DNA synthesis and capsid assembly occur in virus-induced intranuclear structures, termed replication transcription compartments (RTCs). Here we utilised a novel methodology, combining subcellular fractionation quantitative proteomics, to identify cellular proteins which are recruited KSHV-induced RTCs thus play key role replication. We show that several isoforms of the HSP70 chaperone family, Hsc70 iHsp70, redistributed from cytoplasm into nucleus coinciding initial formation RTCs. demonstrate nuclear foci dynamic, initially forming adjacent newly formed RTCs, however during later time points chaperones move within completely co-localise actively replicating DNA. The functional significance Hsp70 recruitment was also examined using specific isoform small molecule inhibitor, VER-155008. Intriguingly, results highlight essential cycle independent protein stability maturation. Notably, inhibition precluded RTC RNA polymerase II (RNAPII) relocalisation genome leading abolishment global subsequent These new findings have revealed mechanisms regulate potential inhibitors as antiviral agents.