Figure 3.

Environmental stimuli alter regulation of RTA to promote KSHV reactivation. Host signaling pathways integrate information about the cellular microenvironment that affects the expression and activity of RTA. Lytic viral proteins promote KSHV reactivation in a feed-forward loop. Various isoforms and posttranslational modifications of LANA switch it from an organizer of latency to a facilitator of the lytic cycle. The cell-intrinsic immune system is antagonized by host and viral factors to augment viral reactivation.