HHV-6 & HIV/AIDS Progression

Both clinical and experimental evidence suggest that HHV-6A may foster the progression of HIV disease toward AIDS. Following the recognition of HHV-6 primary tropism for CD4+ T cells (Lusso 1988), Lusso and colleagues proposed the hypothesis of HHV-6 and HIV-1 working together to deplete CD4+ T cells leading to more immunosuppression and thus catalyzing the progression toward full-blown AIDS. This theory was later corroborated by the observation of synergistic cytopathic effects in primary CD4+ T lymphocytes coinfected in vitro with HHV-6A and HIV-1 (Lusso 1989). HHV-6 not only upregulates the expression of the primary HIV receptor CD4, but also induces functional CD4 in cells that physiologically do not express it (Lusso 1991; Flamand 1998). Through this unique mechanism, HHV-6 may significantly enhance the range of cells susceptible to HIV-1 in vivo, and thus further its spread in coinfected hosts. Several studies also have shown that HHV-6 infection increases production of inflammatory cytokines that enhance in vitro expression of HIV-1, such as TNF-alpha, IL-1 beta, and IL-8 (Flamand 1991; Inagi 1996;Arena 1997).

Unfortunately, these early attempts to link HHV-6 and HIV in vivo were questionable due to the lack of reliable markers as a result of the poor quality of serologic testing available. Recently, the first conclusive in vivo evidence that HHV-6A acts as a promoting factor in the progression of primate immunodeficiency virus disease was observed in experimental coinfection studies in pigtailed macaques (Lusso 2007). Coinfection with HHV-6A was shown to dramatically accelerate the immunological and clinical progression toward full blown AIDS in monkeys infected with a pathogenic simian immunodeficiency virus (SIV) strain and lead to death. Despite these results, further in vivo animal model and patient studies are needed to definitively establish the role of HHV6-A in AIDS.