Mechanism of Inhibition of Viral Lytic Replication by Kaposi’s Sarcoma Associated Herpesvirus Encoded Latency Associated Nuclear Antigen

Ke Lan, MD, PhD

Similar to other herpesvirus, Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV8) can establish a latent infection in the infected host. During latency only a small number of genes are expressed including LANA which is constitutively expressed in cells during latent and lytic infection. LANA was previously shown to be important for establishment of latent episome maintenance through tethering of viral genome to the host chromosomes. Under specific conditions, KSHV can undergo lytic replication with the production of viral progeny. One immediate early gene Rta, encoded by open reading frame 50 of KSHV, has been shown to play a critical role in switching the viral latent replication to lytic replication. Over-expression of Rta from a heterologous promoter is sufficient for driving KSHV lytic replication and the production of viral progeny. We hypothesize that LANA could regulate the expression of Rta and then inhibit virus to undergo lytic replication, So the major goal of this project is to explore how LANA inhibits viral lytic replication by inhibiting expression and antagonizing the function of Rta. We also want to look for some other molecules involved in the latent/lytic switch to elucidate the detailed molecular mechanism by which LANA can maintain the latent infection.