Virology Faculty Member - Kenneth Kaye

Kenneth Kaye

Associate Professor of Medicine

Brigham and Women's Hospital
Infectious Disease
181 Longwood Avenue
Boston, MA 2115
Tel: 617-525-4256
Fax: 617-525-4251
Email: kkaye@rics.bwh.harvard.edu



Our laboratory investigates Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8). KSHV has a causative role in Kaposi's sarcoma, primary effusion lymphomas and multicentric Castleman's disease, an aggressive lymphoproliferative disorder. KSHV latently infects tumor cells and has evolved an intricate mechanism to efficiently persist in proliferating cells in the absence of chromosomal integration. KSHV persists in latently infected cells as an extrachromosomal, multiple copy plasmid (episome), from which it expresses several viral genes including the latency-associated nuclear antigen (LANA). LANA is essential for KSHV episome persistence in cells. LANA mediates viral DNA replication, which occurs in concert with cell DNA replication, and then tethers KSHV episomes to mitotic chromosomes to ensure their efficient segregation to progeny nuclei, thereby avoiding loss of the genome in the cytoplasm. LANA also exerts effects on cell growth and transcription. We are currently investigating the molecular mechanisms underlying LANA’s functions. An understanding of these mechanisms should allow the development of strategies which interrupt LANA function for treatment and prevention of KSHV associated tumors. Our laboratory has also begun to investigate the murine gamma herpesvirus 68 (MHV-68). Similar to KSHV, this virus is a gamma-2 herpesvirus, and encodes a homolog of KSHV LANA. MHV-68 allows investigation of gamma herpesvirus latent infection and presistence in a small animal model.



Last Update: 10/22/2013



Publications

Barbera A, Ballestas ME, Kaye KM. The Kaposi’s sarcoma-associated herpesvirus latency-associated nuclear antigen 1 Nterminus is essential for chromosome association, DNA replication, and episome persistence. J Virol. 2004;78:294-301.

Barbera AJ, Chodaparambil JV, Kelley-Clarke B, Joukov V, Walter JC, Luger K, Kaye KM. The nucleosomal surface as a docking station for Kaposi’s sarcoma herpesvirus LANA. Science 2006;311:856-861.

Kelley-Clarke B, Ballestas ME, Komatsu T, Kaye KM. Kaposi’s sarcoma herpesvirus C-terminal LANA concentrates at pericentromeric and peri-telomeric regions of a subset of mitotic chromosomes . Virology 2007;357:149-157.

Kelley-Clarke B, Ballestas ME, Srinivasan V, Barbera AJ, Komatsu T, Harris T, Kazanjian M, Kaye KM. Separation of the essential KSHV C-terminal LANA domain into chromosome binding and DNA recognition subdomains. J Virol. 2007;81:4348-4356.



© 2013 by the President and Fellows of Harvard College