Kaposi's Sarcoma-Associated Herpesvirus Deregulates Host Cellular Replication during Lytic Reactivation by Disrupting the MCM Complex through ORF59

Abstract

KSHV is the causative agent of various lethal malignancies affecting immunocompromised individuals. Both lytic and latent phases of the viral life cycle contribute to the progression of these cancers. A better understanding of how viral proteins disrupt functions of a normal healthy cell to cause oncogenesis is warranted. One crucial lytic protein produced early during lytic reactivation is the multifunctional ORF59. In this report, we elucidated an important role of ORF59 in manipulating the cellular environment conducive for viral DNA replication by deregulating the normal functions of the host MCM proteins. ORF59 binds to specific MCMs and sequesters them away from replication origins in order to sabotage cellular DNA replication. Blocking cellular DNA replication ensures that cellular resources are utilized for transcription and replication of viral DNA.