Efficient persistence of extrachromosomal KSHV DNA mediated by latency-associated nuclear antigen

Primary effusion Lymphoma (PEL) cells harbor Kaposi's sarcoma-associated he rpesvirus (KSHV) episomes and express a KSHV-encoded Latency-associated nuc lear antigen (LANA). In PEL cells, LANA and KSHV DNA colocalized in dots in interphase nuclei and along mitotic chromosomes. In the absence of KSHV DN A, LANA was diffusely distributed in the nucleus or on mitotic chromosomes. In Lymphoblasts, LANA was necessary and sufficient for the persistence of episomes containing a specific KSHV DNA fragment. Furthermore, LANA colocal ized with the artificial KSHV DNA episomes in nuclei and along mitotic chro mosomes. These results support a model in which LANA tethers KSHV DNA to ch romosomes during mitosis to enable the efficient segregation of KSHV episom es to progeny cells.