[Anti-HIV effects of IFN-tau in human macrophages: role of cellular antiviral factors and interleukin-6].
Tau interferon (IFN-tau) was shown to inhibit human immunodeficiency virus (HIV) replication in vitro more strongly than human IFN-alpha, particularly in human macrophages. IFN-tau efficiently inhibited the early steps of HIV biological cycle, decreasing intracellular HIV RNA and inhibiting the initiation of the reverse transcription of viral RNA into proviral DNA. In this study, the in vitro immunomodulatory effects of IFN-tau were explored in human macrophages. We found that IFN-tau increased the synthesis of the cellular antiviral factors, such as 2',5'-oligoadenylate synthetase/RNase L and MxA protein. These results suggested that IFN-tau induces the same antiviral pathways in macrophages as other type I IFNs. We found that IFN-tau increased the production of interleukins (IL)-10 and IL-6, but not of IL-1ss or TNF-alpha, in not infected and in in vitro HIV-1/Ba-L-infected macrophages. We also found that the neutralization of IL-6 biological activity in the cell culture supernatants of IFN-tau-treated macrophages led to a decrease in the antiretroviral effects of IFN-tau towards HIV RNA. In conclusion, anti-HIV effects of IFN-tau are mediated by several modes of action, mediated either directly by IFN-tau or via other cytokines, such as IL-6, also known to be induced by IFN-alpha.
UPRES EA 220, faculté de médecine Paris Ile-de-France-Ouest, université Versailles St-Quentin, Suresnes, France. bmaneglier@ch-versailles.fr
B
B
Maneglier
C
C
Rogez-Kreuz
N
N
Dereuddre-Bosquet
J
J
Martal
P
P
Devillier
D
D
Dormont
P
P
Clayette
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured / Q000187:drug effects / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D004722:Endoribonucleases / Q000096:biosynthesis / Q000235:genetics; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D016898:Interferon-alpha / Q000502:physiology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D064547:Myxovirus Resistance Proteins; D011257:Pregnancy Proteins / Q000494:pharmacology*; D015728:Receptors, HIV / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*; D000093242:Interleukin-6 Inhibitors
D000911:Antibodies, Monoclonal; D016207:Cytokines; D004722:Endoribonucleases; D019204:GTP-Binding Proteins; D054303:HIV Reverse Transcriptase; D007370:Interferon Type I; D016898:Interferon-alpha; D016753:Interleukin-10; D015850:Interleukin-6; D008070:Lipopolysaccharides; D064547:Myxovirus Resistance Proteins; D011257:Pregnancy Proteins; D015728:Receptors, HIV; D011993:Recombinant Fusion Proteins; D000093242:Interleukin-6 Inhibitors; C508609:IL10 protein, human; C508600:IL6 protein, human; C579071:MX1 protein, human; C020947:interferon tau; C440499:lipopolysaccharide, Escherichia coli O111 B4; C514824:reverse transcriptase, Human immunodeficiency virus 1; C031956:2-5A-dependent ribonuclease
Rôles des facteurs antiviraux cellulaires et de l'interleukine-6 dans les propriétés anti-VIH de l'IFN-tau dans des macrophages humains.