Tumor necrosis factor-alpha/cachectin enhances human immunodeficiency virus type 1 replication in primary macrophages.
Macrophages are important target cells for human immunodeficiency virus type 1 (HIV-1). The ability of HIV-1 to productively infect macrophages may be influenced by endogenous cytokines that alter the activation state of these cells. In this study, the effect of tumor necrosis factor-alpha/cachectin (TNF alpha), a cytokine with macrophage-activating properties, on HIV-1 replication in primary blood monocyte-derived macrophages was examined. Treatment of macrophages with recombinant human TNF alpha (rTNF alpha), starting before or after HIV-1 infection, consistently enhanced viral production fivefold or greater above control (P less than .01). rTNF alpha was active at low concentrations (0.05-50 ng/ml) and increased the replication of both lymphocyte-tropic (human T lymphotropic virus type IIIB) and macrophage-tropic (human T lymphotropic virus type III BaL) strains of HIV-1. These findings provide additional evidence that TNF alpha may play a role in the pathogenesis of HIV-1 infection by upregulating viral expression in macrophages.
Mellors
J W
JW
Department of Internal Medicine and Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut.
Griffith
B P
BP
Ortiz
M A
MA
Landry
M L
ML
Ryan
J L
JL
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha