HHV-8 has been strongly linked to the development of Kaposi's sarcoma with viral DNA sequences found in all forms of the disease. The HHV-8 virus has been shown to infect B cells and to be present in circulating PBMCs of individuals with KS or at high risk for development of KS. The presence of HHV-8 DNA in PBMCs of these individuals however, is sporadic. The relationship between the appearance of HHV-8 in PBMCs and onset of KS is not well understood with the precise timing of a PBMC infection following HHV-8 seroconversion and preceding development of KS not known. Our hypothesis is that HHV-8 viral load within PBMCs will be predictive over time for progression to KS and that the immune status of the individual (measured by CD4 count) will control both the appearance and levels of HHV-8 in these cells. We also predict that the appearance of virus in PBMCs will correlate with rises in antibody titers against lytic and/or latent viral proteins. The goal of the research in this proposal is determine the occurrence rate and viral load of HHV-8 in PBMCs in a longitudinal study of individuals who have seroconverted to HHV-8 during the course of the study. The source of PBMCs for this research will be longitudinal PBMC specimens collected by the Multicenter AIDS Cohort Study (MACS). We will measure the occurrence rate and viral load of HHV-8 in a longitudinal study of PBMCs from MACS subjects who have seroconverted to HHV-8 during their enrollment in the MACS (and the date of seroconversion is known). We will compare results between those individuals who developed KS and those who remained KS-free. These results will also determine the rate of occurrence of detectable levels of HHV-8 DNA in the PBMCs from the time of HHV-8 seroconversion to the onset of KS.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
1R03CA081600-01
Application #
2855276
Study Section
Subcommittee G - Education (NCI)
Program Officer
Starks, Vaurice
Project Start
1999-07-23
Project End
2001-06-30
Budget Start
1999-07-23
Budget End
2000-06-30
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Wang, Q J; Jenkins, F J; Jacobson, L P et al. (2001) Primary human herpesvirus 8 infection generates a broadly specific CD8(+) T-cell response to viral lytic cycle proteins. Blood 97:2366-73