Human astrocytes inhibit HIV-1 expression in monocyte-derived macrophages by secreted factors

Objective: To determine the effects of primary human fetal and adult astroc ytes on HIV-1 replication in monocyte-derived macrophages (MDM). Design: HIV-2 can infect the brain in the early stage of systemic infection . The HIV-1-associated cognitive/motor complex develops later in the course of the disease, suggesting that brain cells may inhibit the early producti ve infection and the development of neurological disease. In this study, we established an in-vitro coculture system to determine whether astrocytes c an modulate HIV-1 replication in MDM. Methods: Elutriated human monocytes were differentiated in culture, then in fected with monocyte tropic HIV-1. One day after infection, MDM were co-cul tured with primary astrocyte. Reverse transcriptase (RT) activity was used to monitor virus replication. RT-polymerase chain reaction (PCR), enzyme-li nked immunosorbent assay (ELISA) and bioassay were used to assess cytokine production. Results: Primary human astrocytes suppressed HIV-1 replication in MDM via t he production of soluble factors. Cytokine inhibitors of HIV-1, such as IFN -gamma, IL-4, IL-10 and IL-13, were not detectable, whereas transforming gr owth factor beta (IGF-P) was constitutively produced only in its latent for m. Paraformaldehyde-fixed astrocytes, unable to secrete cytokines, failed t o inhibit HIV-1. These cells caused enhanced virus replication, however, wh ich correlated with an increase in macrophage colony stimulating factor (M- CSF) production. Conclusions: Human astrocytes can increase and decrease HIV-1 expression in MDM. An imbalance between the positive and negative effects of astrocytes may contribute to the expression of virus in the brain, and the development of HIV-1-associated cognitive/motor complex. (C) 1999 Lippincott Williams & Wilkins..