Kaposis Sarcoma Associated Herpesvirus DNA Replication

Medveczky, Peter Gabor

Abstract

Kaposi's sarcoma associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8) was found in 100% of Kaposi's sarcoma and many body cavity-based lymphomas. It has been hypothesized that KSHV causes these malignancies. KSHV DNA can persist in a latent episomal form and a linear replicative form. The episomal form has been shown to be maintained by the cellular DNA polymerase. It is hypothesized that the episomal viral DNA is maintained by a specific viral origin of replication (ori P) and a DNA binding protein termed trans-activator which is involved in replication of the viral episome.
Three aims are proposed. The first is to identify ori P of KSHV. The second is to map the initiation site and direction of replication.
The third aim i s to search for the transactivator. This study should lead to better understanding of latency.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Cancer Institute (NCI)
• Type: Research Project (R01)
• Project #: 3R01CA075895-04S1
• Application #: 6327336
• Study Section: AIDS and Related Research Study Section 3 (ARRC)
• Project Start: 1997-08-01
• Project End: 2002-05-31
• Budget Start: 2000-06-01
• Budget End: 2002-05-31
• Support Year: 4
• Fiscal Year: 2000
• Total Cost: $68,440

Institution

• Name: University of South Florida
• Department: Biochemistry
• Type: Schools of Medicine
• DUNS #: 069687242
• City: Tampa
• State: FL
• Country: United States
• Zip Code: 33612

Publications

Fejer, Gyorgy; Medveczky, Maria M; Horvath, Elizabeth et al. (2003) The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus interacts preferentially with the terminal repeats of the genome in vivo and this complex is sufficient for episomal DNA replication. J Gen Virol 84:1451-62

Collins, Christopher M; Medveczky, Maria M; Lund, Troy et al. (2002) The terminal repeats and latency-associated nuclear antigen of herpesvirus saimiri are essential for episomal persistence of the viral genome. J Gen Virol 83:2269-78

Collins, Christopher M; Medveczky, Peter G (2002) Genetic requirements for the episomal maintenance of oncogenic herpesvirus genomes. Adv Cancer Res 84:155-74

Lund, T C; Medveczky, M M; Medveczky, P G (1999) Interferon-alpha induction of STATs1, -3 DNA binding and growth arrest is independent of Lck and active mitogen-activated kinase in T cells. Cell Immunol 192:133-9

Lund, T C; Coleman, C; Horvath, E et al. (1999) The Src-family kinase Lck can induce STAT3 phosphorylation and DNA binding activity. Cell Signal 11:789-96

Lund, T C; Prator, P C; Medveczky, M M et al. (1999) The Lck binding domain of herpesvirus saimiri tip-484 constitutively activates Lck and STAT3 in T cells. J Virol 73:1689-94