Viral genome maintenance and latent replication of human gammaherpesviruses

During gammaherpesvirus latency, only a few genes are expressed and required for maintenance of viral latency over a long period. While the expressed latent viral proteins play functional roles in viral latent DNA replication, they do not have replication-associated enzymatic activity such as polymerase or helicase activity. Viral genomes are detected in a similar copy number per infected cell, suggesting that the viral genome is replicated and segregated using host replication machinery. Kaposis sarcoma-associated herpesvirus and EBV have trans-acting elements required for viral genome maintenance during latency; LANA1 and EBNA1, respectively. The proteins recruit host replication-associated proteins at their latent origins, leading to initiation of viral replication and segregation with host chromosomes once per cell cycle. In addition, viral latent origins (cis-elements) provide trans-element-binding sites as well as a sufficient space for recruitment of cellular factors. In this review, we describe the molecular mechanisms required for replication of the viral genome during latency, including interactions with cellular factors and the interplay between viral trans- and cis-elements.