HIV-1 INDUCES TUMOR-NECROSIS-FACTOR AND IL-1 GENE-EXPRESSION IN PRIMARY HUMAN MACROPHAGES INDEPENDENT OF PRODUCTIVE INFECTION

Cytokines such as tumour necrosis factor-alpha (TNF-alpha) and IL-1 be ta may play a role in immunopathogenesis of AIDS. We studied early eff ects (0.5-48 h) of monocytotropic (ADA) or lymphotropic (IIIB) strains of HIV-1 on TNF-alpha and IL-1 beta mRNA expression in primary human macrophages by a semi-quantitative reverse transcriptase-polymerase ch ain reaction (RT-PCR) assay. Three-day-old monocyte-derived macrophage s were exposed either to tissue culture supernatants containing virus (at multiplicity of infection (m.o.i.) of 0.05) or to control supernat ants free of virions and gp 120. ADA strain, but not IIIB, replicated in primary tissue culture-differentiated macrophages (TCDM). Soluble C D4 (sCD4) was used to inhibit binding of both strains to macrophages. We found that TNF-alpha and IL-1 beta gene expression was induced by b oth strains 0.5-3h after addition of virus, and that enhanced expressi on of both cytokines was inhibited by sCD4. We conclude that CD4-depen dent binding to the cell surface is sufficient to enhance TNF-alpha an d IL-1 beta mRNA, whereas productive viral replication in primary huma n macrophages is not required. Therefore, similar pathways regulate ge ne expression of TNF-alpha and IL-1 beta by macrophages during initial infection by HIV-1 in vitro.