Human herpesvirus 8 (HHV-8), also called Kaposi's sarcoma- associated virus (KSHV), was first identified in 1994 in AIDS Kaposi's sarcoma biopsies. Kaposi's sarcoma (KS) was a relatively rare angiogenic neoplasm that dramatically increased in incidence with the onset of the AIDS epidemic. Approximately 20 percent of gay and bisexual men with AIDS develop KS. HHV-8 is also consistently assoicated with two other malignancies in AIDS patients: Multicentric Castleman's disease and a subset of non-Hodgkin's lymphomas called primary effusion lymphomas (PELs) or body cavity based lymphomas (BCBLs). PELs have the unusual feature that the majority are co-infected with both HHV-8 and another human gamma herpesvirus Epstein-Barr virus (EBV). HHV-8 and EBV each encode multiple growth stimulatory genes and the potential exists for inter-virus interactions that modulate the program of HHV-8 or EBV gene expression to allow the development of this particular malignancy. A goal of this research project is to better understand the consequences of dual infection in PELs. LANA is one of the few HHV-8 genes that is expressed in latent infection and in all HHV-8 associated tumor cells. LANA's role in the maintenance of HHV-8 latency and in PEL cell development will be explored.
The Specific Aims of this proposal are:
Aim 1. EBV latency gene expression, promoter usage, genome copy number and status (episomal or integrated) will be examined in PEL cell lines. The possibility that HHV-8 LANA can modulate EBV latency promoter activity will be examined.
Aim 2. A genetic assay for the contribution of HHV-8 latency genes to PEL development will be established.
Aim 3. The HHV-8 latency protein LANA will be characterized to determine its contribution to HHV-8 latency DNA replication and its potential contribution to tumorigenesis through modulation of cellular gene expression.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA085151-03
Application #
6489366
Study Section
Special Emphasis Panel (ZRG1-AARR-2 (01))
Program Officer
Read-Connole, Elizabeth Lee
Project Start
2000-01-19
Project End
2004-12-31
Budget Start
2002-01-01
Budget End
2002-12-31
Support Year
3
Fiscal Year
2002
Total Cost
$270,727
Indirect Cost
Name
Johns Hopkins University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218