VIROLOGICAL AND MOLECULAR-PARAMETERS OF HIV-1 INFECTION OF HUMAN EMBRYONIC ASTROCYTES

Two different strains of HIV-1, the lymphotropic HIV-IIIB and the mono cytotropic HIV-Ba-L, were able to infect tertiary cultures of astrocyt es established from the human embryonic brain. The infection did not r equire contact with infected cells, as astrocytes were exposed to infe ctious cell-free supernatants. Except for an early transient peak of p 24 consistently observed after infection with HIV-Ba-L, the infection of astrocytes appeared to be nonproductive. However, viral production was always observed when infected astrocytes were cocultured with perm issive cells (CEM-SS or monocytes). To exclude the possibility that un detectable levels of virus are chronically produced by astrocytes, we exposed permissive cells to p24 negative supernatants taken from infec ted cultures. In such conditions permissive cells were never infected. Infection of astrocytes by HIV-1 was further supported by the finding that provirus persisted in these cells. Indeed, by a nested PCR, we d etected HIV-1 DNA even one month after infection. Moreover, at the tra nscriptional level we observed expression of the multiply spliced RNA (tat and nef primers). Noteworthy, this pattern of HIV-1 expression di d not change appreciably when astrocytes were pretreated and cultivate d in the presence of IL-1 beta. Altogether, our data support the conce pt that astrocytes may play a role in the spread of HIV-1 infection wi thin the brain and in the pathogenesis of neuro-AIDS.