Objectives:HIV-2 can use a broader range of co-receptors than HIV-1in vitro, and is less dependent on CD4 for infection. The aim of this study was to detect productive HIV-2 infection in the brain and investigate whether HIV-2 has an expanded tropism for brain cellsin vivo, in comparison with HIV-1, which productively infects macrophages/microglia.Design:Brain samples taken at autopsy from eight patients who died from AIDS, six HIV-2 and two HIV-1/HIV-2 dually seropositive, with HIV encephalitis (HIVE), collected in Abidjan, Côte d'Ivoire in 1991, were examined for the presence and localization of productive HIV-2 infection.Methods:Using immunohistochemistry, the presence of HIV-2 p26 in formalin-fixed, wax-embedded brain tissue sections was investigated. Double-staining with glial fibrillary acidic protein (GFAP), CD45- and CD68-specific antibodies was performed to identify infected cell types.Results:HIV-2 p26 was detected in brain tissue from four of the HIV-2 cases and one of the dually infected individuals. The productively infected cells were either microglia or infiltrating macrophages.Conclusions:The productively infected cells in the brains of HIV-2 infected individuals are macrophages/microglia. No evidence was found for productive infection of astrocytes, neurons or oligodendrocytes. Thus, the broaderin vitrocell tropism, promiscuous coreceptor usage and relative independence of CD4 by HIV-2 compared to HIV-1 does not broaden its range of target cells in the brain.