Kenneth M. Kaye, MD
My laboratory investigates Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8). KSHV has a causative role in Kaposi's sarcoma, the leading AIDS malignancy, and is also tightly linked with primary effusion lymphoma and multicentric Castleman's disease. KSHV infection is predominantly latent in tumors. In latently infected cells, KSHV persists as an extrachromosomal, multiple copy plasmid (episome). Persistence of episomes in rapidly proliferating cells requires a carefully orchestrated series of events. KSHV DNA must replicate in concert with cellular DNA and then efficiently partition to progeny nuclei. The latency-associated nuclear antigen (LANA) is necessary and sufficient for KSHV episome persistence in the absence of other viral genes. LANA binds specific sequence in KSHV DNA to mediate its replication. LANA then simultaneously binds viral DNA and mitotic chromosomes to segregate the episomes to daughter nuclei. We are currently investigating the molecular mechanisms underlying these LANA functions. We recently found that LANA attaches to chromosomes by directly binding histones H2A/H2B. A more precise understanding of LANA function may lead to strategies that allow for treatment and prevention of KSHV associated tumors.