HIV-1 induces tumour necrosis factor and IL-1 gene expression in primary human macrophages independent of productive infection

SUMMARYCylokines such as tumour necrosis factor-alpha (TNF-a) and IL-Iβ may play a role in immunopalhogcncsis of AIDS, We studied early effects (05-48 h) of monocytotropic (ADA) or tymp ho tropic (1MB) strains of HIV-1 on TNF-α and IL-1β mRNA expression in primary human macrophages by a semi-quantitative reverse transcriptase-polymcrase chain reaction (RT-PCR) assay. Three-day-old monocyte-derived macrophages were exposed either to tissue culture supernatants containing virus (at multiplicity of infection (m.o.i.) of 005) or to control supernatants frceofvirionsandgpI20. ADA strain, but not IIIB. replicated in primary tissue culture-differentiated macrophages (TCDM). Soluble CD4 (sC D4) was used to inhibit binding of both strains to macrophages. We found that TNF-arand IL-lβ gene expression was induced by both strains 0-5-3 hafter addition of virus, and that enhanced expression of both cytokines was inhibited by sCD4. We conclude that C D4-dependcnl binding lo ihc cell surface is sufficient to enhance TNI′-α and ll.-lβ mRNA. whereas productive viral replication in primary human macrophages is not required. Therefore, similar pathways regulate gene expression of TNF-a and IL-Iβ by macrophages during initial infection by HIV-1 in vitro.