The eighth human herpesvirus (HHV-8) was identified, recently, by recovery of viral DNA fragments in AIDS-related Kaposi's sarcomas (KSs). HHV-8 has now been identified in all forms of KS. A sexual route of HHV-8 transmission has been suggested by several studies performed in the United States, where homosexual and parental exposure are the predominant routes of HIV transmission. Currently, the mode of transmission of HHV-8 infection in Africa, where HIV is transmitted heterosexually and KS is endemic, is unknown. Several HHV-8-positive cell lines have been established from patients with HIV-related HHV-8-positive body-cavity based lymphomas. HHV-8 cloned from one such line has now been almost entirely sequenced and a preliminary characterization of the open reading frames completed. However, in a number of previous instances prototype isolates of other viruses have differed significantly from wild-type isolates. Studies examining the genomic diversity of HHV-8 have not been published. How well the laboratory established clones of HHV-8 from the United States will represent wild-type virus is completely unknown. In order to answer these two important unanswered questions the Investigator and her associates will analyze an existing, unique collection of blood and semen samples from Malawi. The hypothesis is that HHV-8 is a sexually-transmitted infection acquired by way of both heterosexual and homosexual contact, is highly endemic in central Africa, and transmission is influenced by the presence of genital inflammation. A second hypothesis is that genetic diversity exists in HHV-8 and that accurate interpretation of functional studies of HHV-8 proteins will await information regarding the degree to which the laboratory strains represent clinical isolates of HHV-8.
Specific Aim #1 : To determine the prevalence of seroreactivity to latent, lytic, and immediate-early HHV-8 antigens in populations of male patients and blood donors seen at a Malawi hospital.
Specific Aim #2 : To identify factors which are associated with HHV-8 seroreactivity.
Specific Aim #3 : To determine the frequency of HHV-8 DNA shedding in semen.
Specific Aim #4 : To identify factors which influence the presence of HHV-8 DNA in the semen.
Specific Aim #5 : To determine the diversity of HHV-8 isolates in the Malawi cohort as compared to the prototype HHV8.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA075976-02
Application #
2748975
Study Section
AIDS and Related Research Study Section 2 (ARRB)
Program Officer
Starks, Vaurice
Project Start
1997-08-05
Project End
2001-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599