Leao, Jair Carneiro; (1999) Studies into the in vivo interactions between human immunodeficiency virus and human herpesvirus 8. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

In HIV-coinfected people unaffected by Kaposi sarcoma (KS), circulating HHV-8 DNA and anti-HHV-8 antibodies are detected particularly frequently and at high levels. Studies were conducted to determine whether HHV-8 hyperactivity in such individuals could be the consequence of immunosuppression-associated reactivation, transactivation by HIV or the propensity of the host to multiple HHV-8 infection. HHV-8 subgenomic DNA was amplified by PCR from peripheral blood of HIV-infected patients, health care workers and patients who had undergone bone marrow transplantation (BMT), and from oral lesional tissues of patients with AIDS-associated KS. Clones derived from amplicons originating from DNA fragments in open reading frame (ORF) 26 and ORF K1 were isolated. For each ORF, intra-specimen nucleotide sequence differences were determined. The extent of HHV-8 variation in clones derived from blood of HIV-positive patients was significantly higher than in blood from health care workers or post-BMT patients or in AIDS-KS lesional tissue. Among the clones derived from the latter three categories of specimens, sequence variations were not significantly different. To investigate if HIV plays a role in inducing HHV-8 hyperactivity, the frequency of circulating HHV-8 DNA, HIV load, anti-HHV-8 antibody level and CD4+ T cell counts was studied before and after therapy with protease inhibitors. While there was an increase in the CD4+ T cell counts and a Studies into the in vivo interactions between HIV and HHV-8 decrease in HHV-8 DNA, no significant differences in the other variables were observed. The findings of this study suggest that HIV-infected individuals tend to be multiply-infected with HHV-8, that each AIDS-KS lesion is associated with infection by a single HHV-8 variant or a small group of related variants, and that HIV may influence, or be associated with the replication of HHV-8.

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