Tumor Necrosis Factor- /Caehectin Enhances Human Immunodeficiency Virus Type 1 Replication in Primary Macrophages

Abstract

Macrophages are important target cells for human immunodeficiency virus type 1 (HIV-1). The ability of HIV-1 to productivelyinfect macrophages may be influenced byendogenous cytokines that alter the activation state of these cells. In this study, the effect of tumor necrosis factor-α/cachectin (TNFα), a cytokine with macrophage-activating properties, on HIV-l replication in primary blood monocyte-derived macrophages wasexamined. Treatment of macrophages with recombinant human TNFα (rTNFα), starting before or after HIV-1 infection, consistently enhanced viral production fivefoldor greater above control (P < .01). rTNFα was active at low concentrations (0.05–50 ng/mI) and increased the replication of both lymphocyte-tropic (human T lymphotropic virus type III_B) and macrophage-tropic (human T lymphotropic virus type III BaL) strains of HIV-1. These findings provide additional evidence that TNFα may playa role in the pathogenesis of HIV-1 infection by upregulating viral expression in macrophages.