HIV-1 GENE-EXPRESSION AND REPLICATION IN NEURONAL AND GLIAL-CELL LINES WITH IMMATURE PHENOTYPE - EFFECTS OF NERVE GROWTH-FACTOR

Encephalopathy and neurological disorders are a major manifestation of pediatric AIDS. Although HIV-1 can replicate in cells of neuronal and glial origin, it is yet unclear whether immature neural cells, which are present during nervous system development, can support HIV-1 repli cation and whether neurotrophic factors can modulate HIV-1 gene expres sion. In this study we show that a glial cell line with a phenotype cl osely resembling immature glial cells is more permissive to HIV-1 infe ction and replication than a neuroblastic cell line. After HIV-1 infec tion or after transfection of these cells with the HIV-1 LTR-CAT repor ter gene alone or in the presence of Tat, both HIV-1 replication and v iral gene expression progressively decrease in the neuronal cell line, while they increase in the glial cell line. In both cell types viral gene expression and replication are augmented by the addition to the c ells of nerve growth factor (NGF) at concentrations which induce neuro nal differentiation. However, these effects are again more evident wit h the glial cell type, suggesting that immature glial cells may repres ent one of the major targets and reservoirs of HIV-1 in the developing nervous system. As NGF and Tat act synergistically in inducing HIV-1 gene expression, these data also suggest that during development the p resence of high levels of neural trophic factors may activate viral re plication and render the CNS more susceptible to the deleterious effec ts of HIV-1 infection. (C) 1994 Academic Press, Inc.