Human immunodeficiency virus replication induces monocyte chemotactic protein-1 in human macrophages and U937 promonocytic cells

We have recently described a significant correlation between human immunode ficiency virus-1 (HIV-1) RNA replication and monocyte chemotactic protein-1 (MCP-1) levels in the cerebrospinal fluid (CSF) of individuals with the ac quired immunodeficiency syndrome (AIDS) with HIV encephalitis (E). Because local macrophages (microglia) are the cells predominantly infected in the b rain, we investigated whether in vitro HIV infection affects MCP-1 producti on in mononuclear phagocytes (MP). MCP-1 secretion and expression were cons instently upregulated over constitutive levels in human monocyte-derived ma crophages (MDM) infected with the M-tropic R5 Bat strain of HIV-1. HIV repl ication was required for this effect, as demonstrated by the absence of che mokine upregulation after infection in the presence of 3'-azido-3'-deoxythi midine (AZT) or cell-exposure to heat-inactivated (Delta degrees) virus. MC P-1 induction was not restricted to HIV-1 Bat, but was also observed during productive infection of MDM with two primary isolates differing for entry coreceptor usage and of U937 cells with the X4 HIV-1 MN strain. Based on th e observation that exogenous HIV-1 Tat induced MCP-1 expression in astrocyt es, we also investigated its role in MDM and U937 cells. Exogenous Tat indu ced MCP-1 production from MDM in a concentration-dependent manner, however, it was not effective on uninfected U937 cells or on the chronically infect ed U937-derived cell line U1. Transfection of Tat-expressing plasmids moder ately activated HIV expression in U1 cells, but failed to induce MCP-1 expr ession in this cell line or in uninfected U937 cells. HIV replication-depen dent expression of MCP-1 in MP may be of particular relevance for the patho genesis of HIV infection in nonlymphoid organs such as the brain. (C) 1999 by The American Society of Hematology.