Nonproductive human immunodeficiency virus type 1 infection of human fetalastrocytes: Independence from CD4 and major chemokine receptors

Human immunodeficiency virus type 1 (HIV-1) infection of the brain is assoc iated with neurological manifestations both in adults and in children. The primary target for HIV-1 infection in the brain is the microglia, but astro cytes can also be infected. We tested 26 primary HIV-1 isolates for their c apacity to infect human fetal astrocytes in culture. Eight of these isolate s, independent of their biological phenotype and chemokine receptor usage, were able to infect astrocytes. Although no sustained viral replication cou ld be demonstrated, the virus was recovered by coculture with receptive cel ls such as macrophages or on stimulation with interleukin-1 beta. To gain k nowledge into the molecular events that regulate attachment and penetration of HIV-1 in astrocytes, we investigated the expression of several chemokin e receptors. Fluorocytometry and calcium-mobilization assay did not provide evidence of expression of any of the major HIV-1 coreceptors, including CX CR4, CCR5, CCR3, and CCR2b, as well as the CD4 molecule on the cell surface of human fetal astrocytes. However, mRNA transcripts for CXCR4, CCR5, Bonz o/STRL33/TYMSTR, and APJ were detected by RT-PCR. Furthermore, infection of astrocytes by HIV-I isolates with different chemokine receptor usage was n ot inhibited by the chemokines SDF-1 beta, RANTES, MIP-1 beta, or MCP-1 or by antibodies directed against the third variable region or the CD4 binding site of gp120. These data show that astrocytes can be infected by primary HIV-I isolates via a mechanism independent of CD4 or major chemokine recept ors. Furthermore, astrocytes are potential carriers of latent HIV-1 and on activation may be implicated in spreading the infection to other neighbouri ng cells, such as microglia or macrophages. (C) 1999 Academic Press.