Suboptimal and optimal activation signals modulate differently the expression of HIV-1 and cytokine genes.
Expression of HIV-1 and cytokine genes was investigated in chronically infected lymphocytic and promonocytic cell lines. As in normal human peripheral blood lymphocytes (PBL), a suboptimal activation signal with phorbol myristate acetate (PMA) did not trigger significant cytokine expression, whereas optimal activation signal (PMA + ionomycin) did. In contrast, a suboptimal activation was sufficient to up-regulate expression of HIV transcripts with kinetics similar to that observed in cells infected de novo by HIV. The level of HIV RNA in the promonocytic line was very low and markedly delayed when compared to the lymphocytic lines. We concluded that HIV induction required weaker activation signals than cytokine induction and that kinetics and level of HIV expression were not modified by induction of these cytokines. However, HIV expression appeared to alter the regulation of genes involved in proliferation and functional differentiation such as a decreased expression of IL-2 and IL-2R alpha and an increased expression of IFN gamma and TNF alpha mRNA.
Serpente
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Laboratoire d'Immunologie et d'Oncologie des Maladies Rétrovirales, INSERM U152, Institut Cochin de Génétique Moléculaire, Paris, France.
Sitbon
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Vaquero
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D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001483:Base Sequence; D017252:CD3 Complex; D002460:Cell Line; D016207:Cytokines / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D007700:Kinetics; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014764:Viral Proteins / Q000235:genetics / Q000302:isolation & purification
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D016207:Cytokines; D007376:Interleukin-2; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D012367:RNA, Viral; D011948:Receptors, Antigen, T-Cell; D014764:Viral Proteins; D013755:Tetradecanoylphorbol Acetate