Transforming growth factor beta suppresses human immunodeficiency virus expression and replication in infected cells of the monocyte/macrophage lineage.
The pleiotropic immunoregulatory cytokine transforming growth factor beta (TGF-beta) 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-beta 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-beta suppressed PMA induction of HIV transcription in U1 cells. In contrast, TGF-beta did not significantly affect the expression of HIV induced by tumor necrosis factor alpha (TNF-alpha). These suppressive effects were not mediated via the induction of interferon alpha (IFN-alpha). TGF-beta 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-beta were observed in either a chronically infected T cell line (ACH-2) or in primary T cell blasts infected in vitro. Therefore, TGF-beta may play a potentially important role as a negative regulator of HIV expression in infected monocytes or tissue macrophages in infected individuals.
Poli
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Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Kinter
A L
AL
Justement
J S
JS
Bressler
P
P
Kehrl
J H
JH
Fauci
A S
AS
D000998:Antiviral Agents; D002460:Cell Line; D002478:Cells, Cultured; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D007700:Kinetics; D008264:Macrophages; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D015850:Interleukin-6; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D016212:Transforming Growth Factor beta; D014764:Viral Proteins; D013755:Tetradecanoylphorbol Acetate