FIG. 10.

Proposed role of Hey1 in KSHV reactivation and lytic replication. During latency the RTA promoter is tightly repressed by the Hey1-induced repressosome and other repressors (indicated as a complex to the left of the Hey1 repressosome), preventing RTA expression. Upon plasma cell differentiation, XBP-1s is expressed and activates the RTA promoter, causing low-level RTA expression and thus triggering initial lytic reactivation. Once a small amount of RTA is expressed, it ubiquitinates Hey1, leading to proteasomal degradation of Hey1 and dissociation of the repressosome from the RTA promoter. Loss of the Hey1-induced repressosome from the RTA promoter enhances RTA expression, allowing complete lytic replication to proceed. Ub, ubiquitin.