Transforming growth factor β suppresses human immunodeficiency virus expression and replication in infected cells of the monocyte/macrophage lineage

Abstract

The pleiotropic immunoregulatory cytokine transforming growth factor β (TGF-β) potently suppresses production of the human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome, in the chronically infected promonocytic cell line U1. TGF-β significantly (50-90%) inhibited HIV reverse transcriptase production and synthesis of viral proteins in U1 cells stimulated with phorbol myristate acetate (PMA) or interleukin 6 (IL-6). Furthermore, TGF-β suppressed PMA induction of HIV transcription in U1 cells. In contrast, TGF-β did not significantly affect the expression of HIV induced by tumor necrosis factor α (TNF-α). These suppressive effects were not mediated via the induction of interferon a (IFN-α). TGF-β also suppressed HIV replication in primary monocyte-derived macrophages infected in vitro, both in the absence of exogenous cytokines and in IL-6-stimulated cultures. In contrast, no significant effects of TGF-β were observed in either a chronically infected T cell line (ACH-2) or in primary T cell blasts infected in vitro. Therefore, TGF-β may play a potentially important role as a negative regulator of HIV expression in infected monocytes or tissue macrophages in infected individuals.