Lack of a mechanism for faithful partition and maintenance of the KSHV genome

Kaposi's sarcoma-associated herpesvirus (KSHV) is a causative agent for some tumors. The virus establishes latency in infected cells, where its genomes are often present as episomes and replicate in a cell-cycle-dependent manner, apparently maintaining the same copy number. LANA and TR are key KSHV replication factors, and we hypothesized that they also function in viral genome maintenance. We cloned a bacmid containing the viral TR region from PEL cells and tested whether TR with LANA were sufficient for viral genome maintenance. However, neither the TR region nor even the full KSHV genome cloned into a bacmid were maintained in cultured cells, except when they were grown under selective pressure. Thus, no specific viral mechanism for the faithful partitioning and maintenance of the KSHV genome is likely to exist. KSHV might confer a positive growth effect on infected PEL cells, but not on immortalized or transformed cells previously uninfected by KSHV.