Abstract 901 Poster Session IV, Tuesday, 5/4 (poster 117)

Chemokines are involved in the migration of inflammatory cells and have been implicated in different inflammatory processes in the central nervous system (CNS). CCR5 is a chemokine receptor that functions as a coreceptor on CD4+ T-lymphocytes and macrophages for macrophage tropic (M-tropic) HIV strains especially during the early stages of HIV infection. The regulation of CCR5 expression may affect infection of these cells by HIV and therefore AIDS pathogenesis. We report here that fetal human astrocytes express CCR5 under normal culture conditions as shown by RT-PCR of total mRNA. CCR5 expression was downregulated in astrocyte cultures by agents that increase intracellular levels of cAMP such as the prostaglandins PGE1, PGE2 and PGF1α. Ethidium-Bromide stained gel electrophoresis of RT-PCR products showed the absence of CCR5 signal after 18hrs of incubation with prostaglandins. However, after 7 days of incubation of astrocyte cultures with HIV monotropic JR strain and prostaglandins, no inhibition of HIV infection was noted as shown by positive HIV DNA PCR in all cultures. Our results suggest that although prostaglandins can downregulate HIV coreceptor (CCR5) expression in human astrocytes, they are unable to block infection by a monotropic strain of HIV. This suggests other coreceptors, yet to be identified, are involved in HIV infection of the CNS and in neuroAIDS pathogenesis.

This study was supported by USPHS grant MH 46815 and the Children's Hospital of Michigan endowment fund.