Tumour necrosis factors (α, β) induced by HIV-1 in peripheral blood mononuclear cells potentiate virus replication

Abstract

Cytokines such as tumour necrosis factor (TNF) can induce HIV-1 production in T-cell tumour lines. However, it is not known if the same occurs in freshly isolated mononuclear cells, nor is it known if the virus can itself regulate cellular cytokine production. In this paper we report that HIV-1 induces peripheral blood mononuclear cells (PBMC) and CD4+ T lymphocytes to secrete TNFα, TNFβ and interferon-gamma (IFNγ), three cytokines having multifunctional activities and complex physiological roles. We also show that separate addition of exogenous recombinant (r) TNFα or rTNFβ or rlFNγ increases HIV-1-induced syncytium formation in both PBMC and CD4+ cells by up to 10 000-fold, with TNFα being most potent in this regard. Finally, we show that syncytium formation induced by diverse HIV-1 isolates and LAV-2 is inhibited without the addition of exogenous r-cytokines by the respective anti-cytokine antibodies. Our study therefore demonstrates that efficient HIV replication in primary mononuclear cells is associated with the ability of the virus to induce TNF and IFNγ secretion.