Induction of human immunodeficiency virus 1 replication by human herpesvirus 8

Background-Human immunodeficiency virus 1 (HIV1)-infected individuals are c ommonly infected with herpesviruses, including cytomegalovirus, herpes simp lex virus, varicella-zoster virus, and human herpesvirus 8 (HHV-8, also kno wn as Kaposi sarcoma-associated herpesvirus [KSHV]). Previous studies have demonstrated that coinfection with herpesviruses can modulate HIV-1 replica tion. This can occur either through direct interaction between the 2 viruse s or through secondary effects resulting from the release of cellular facto rs in response to infection. Objective - To investigate HIV-1 replication in the presence and absence of HHV-8. Design and Methods - HIV-1 replication was analyzed following culture of HI V-1-infected CD4(+) T cells in the presence of HHV-8 infected B-cell lines or control, uninfected B-cell lines. To confirm and extend the results of t hese in vitro studies, HIV-1-infected T cells were injected into human skin transplanted onto severe combined immunodeficient mice. The human skin was also injected with purified HHV-8 or phosphate-buffered saline as a contro l and HIV replication measured in biopsy specimens taken 5 to 8 days later. Results and Conclusions - The results demonstrated a significant increase i n HIV-1 replication in the presence of HHV-8 in both the in vitro and in vi vo model systems. Although the mechanism responsible for HHV-8 induction of HIV-1 replication remains to be identified, the results indicate that thes e 2 viruses may interact at the molecular level in coinfected patients, res ulting in increased HIV-1 viral load.