Induction of NF-[chi]B during monocyte differentiation is associated with activation of HIV-gene expression

Abstract

Cells of the monocyte-macrophage lineage are important targets of HIV infection. We report here that the phenotypic differentiation of monocyte cell lines induced by phorbol esters or tumour necrosis factor [alpha] (TNF[alpha]) is associated with expression of nuclear factor kappa B (NF-[chi]B). In parallel with such differentiation, HIV transcription, monitored using an HIV long terminal repeat reporter gene construct, is activated in such cells under the influence of enhanced NF-[chi]B expression. Also, in a promonocyte cell line chronically infected with HIV, NF-[chi]B expression and HIV transcription were enhanced on stimulation with phorbol ester or TNF[alpha]. Thus, stimulation of monocyte cell lines by phorbol esters or TNF[alpha] induces cell differentiation and activates HIV transcription. Such a process may have fundamental implications in AIDS pathogenesis in vivo and may be important in disease progression induced by opportunistic infections directly or indirectly involving macrophages.