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.
| Quinlivan, E Byrd; Zhang, Chuan; Stewart, Paul W et al. (2002) Elevated virus loads of Kaposi's sarcoma-associated human herpesvirus 8 predict Kaposi's sarcoma disease progression, but elevated levels of human immunodeficiency virus type 1 do not. J Infect Dis 185:1736-44 |
| Quinlivan, E B; Wang, R X; Stewart, P W et al. (2001) Longitudinal sero-reactivity to human herpesvirus 8 (KSHV) in the Swiss HIV Cohort 4.7 years before KS. J Med Virol 64:157-66 |
