DESCRIPTION (adapted from the Abstract): 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
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.
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