Fine-Tuning of the Kaposi's Sarcoma-Associated Herpesvirus Life Cycle in Neighboring Cells through the RTA-JAG1-Notch Pathway.

ABSTRACT: Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is an oncogenic pathogen that displays latent and lytic life cycles. In KS lesions, infiltrated immune cells, secreted viral and/or cellular cytokines, and hypoxia orchestrate a chronic pro-lytic microenvironment that can promote KSHV reactivation. However, only a small subset of viruses spontaneously undergoes lytic replication in this pro-lytic microenvironment while the majority remains in latency. Here, we show that the expression of the Notch ligand JAG1 is induced by KSHV-encoded replication and transcription activator (RTA) during reactivation. JAG1 up-regulation activates Notch signaling in neighboring cells and prevents viral lytic replication. The suppression of JAG1 and Notch1 with inhibitors or small interfering RNA promotes l

SUBMITTER: Li S 

PROVIDER: S-EPMC5070770 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature