The regulation of KSHV lytic reactivation by viral and cellular factors

Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus that exhibits two distinct phases of infection in the host-latent and lytic. The quiescent latent phase is defined by limited expression of a subset of viral proteins and microRNAs, and an absence of virus production. KSHV periodically reactivates from latency to undergo active lytic replication, leading to production of new infectious virions. This switch from the latent to the lytic phase requires the viral protein regulator of transcription activator (RTA). RTA, along with other virally encoded proteins, is aided by host factors to facilitate this transition. Herein, we highlight the key host proteins that are involved in mediating RTA activation and KSHV lytic replication and discuss the cellular processes in which they function. We will also focus on the modulation of viral reactivation by the innate immune system, and how KSHV influences key immune signaling pathways to aid its own lifecycle.