Human Leydig cells are productively infected by some HIV-2 and SIV strains but not by HIV-1

OBJECTIVES: With the use of highly active antiretroviral therapy, the identification of HIV reservoirs within the body has become an important issue. However, the testis has been largely ignored despite representing a pharmacologic sanctuary which could act as a viral reservoir. DESIGN: Because alterations in testosterone production have frequently been reported in HIV-infected individuals, we investigated whether the testosterone-producing Leydig cells could become directly infected by HIV-1, HIV-2 or SIV. METHODS: Purified Leydig cells were infected with a panel of HIV-1, HIV-2 and SIV strains and examined for expression of HIV/SIV receptors. Additionally, the impact of CD4 transduction on Leydig cell infection was determined. RESULTS: Leydig cells were unable to support productive infection of the seven HIV-1 isolates tested. No CD4, CXCR4 or CCR5 expression was evident on the surface of Leydig cells and transduction with a CD4 expressing adenovirus did not induce HIV-1 infection. In contrast, some primary and laboratory adapted CD4-independent HIV-2 and SIV strains were able to enter and replicate productively in Leydig cells. CONCLUSIONS: Our results suggest that Leydig cells do not represent a target for HIV-1 infection within the testis. In contrast, Leydig cells support HIV-2 and SIV infection and thus represent a potential target for infection. Receptor use and significance of HIV-2/SIV infection of Leydig cells remain to be determined.