Interleukin-27 is a potent inhibitor of cis HIV-1 replication in monocyte-derived dendritic cells via a type I interferon-independent pathway

• Published in: PloS one Vol. 8; no. 3; p. e59194
• Main Authors: Chen, Qian, Swaminathan, Sanjay, Yang, De, Dai, Lue, Sui, Hongyan, Yang, Jun, Hornung, Ronald L, Wang, Yanmei, Huang, Da Wei, Hu, Xiaojun, Lempicki, Richard A, Imamichi, Tomozumi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.03.2013; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; Antigens; Antiviral agents; Bioinformatics; Biological response modifiers; Biology; Blotting, Western; Cancer; CCR5 protein; CD4 antigen; Cell Differentiation - immunology; Cytokines; Cytokines - metabolism; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - metabolism; DNA microarrays; Flow Cytometry; Gene expression; Granulocyte-macrophage colony-stimulating factor; Health aspects; HIV; HIV-1 - drug effects; HIV-1 - growth & development; Human immunodeficiency virus; Humans; Immune system; Immunology; Infection; Infections; Inflammation; Inhibition; Inhibitors; Interferon; Interferon Type I - metabolism; Interleukin; Interleukin 12; Interleukin 23; Interleukin 27; Interleukin 4; Interleukin-17 - pharmacology; Interleukins; Laboratories; Lipopolysaccharides; Lymphatic system; Lymphocytes; Lymphocytes T; Macrophages; Medical research; Medicine; Microarray Analysis; Monocytes; Monocytes - cytology; Monocytes - immunology; Neutralization; Real-Time Polymerase Chain Reaction; Replication; Reverse transcription; Science; T cells; Virus replication; Virus Replication - drug effects; Viruses; United States > US; Maryland
• DOI: 10.1371/journal.pone.0059194
• ISSN: 1932-6203

IL-27, a member of the IL-12 family of cytokines, plays an important and diverse role in the function of the immune system. Whilst generally recognized as an anti-inflammatory cytokine, in addition IL-27 has been found to have broad anti-viral effects. Recently, IL-27 has been shown to be a potent inhibitor of HIV-1 infection in CD4+ T cells and macrophages. The main objective of this study was to see whether IL-27 has a similar inhibitory effect on HIV-1 replication in dendritic cells (DCs). Monocytes were differentiated into immature DCs (iDCs) and mature DCs (mDCs) with standard techniques using a combination of GM-CSF, IL-4 and LPS. Following differentiation, iDCs were infected with HIV-1 and co-cultured in the presence or absence of IL-27. IL-27 treated DCs were shown to be highly potent inhibitors of cis HIV-1, particularly of CCR5 tropic strains. Of note, other IL-12 family members (IL-12, IL-23 and IL-35) had no effect on HIV-1 replication. Microarray studies of IL-27 treated DCs showed no up-regulation of Type I (IFN) gene expression. Neutralization of the Type-I IFN receptor had no impact on the HIV inhibition. Lastly, IL-27 mediated inhibition was shown to act post-viral entry and prior to completion of reverse transcription. These results show for the first time that IL-27 is a potent inhibitor of cis HIV-1 infection in DCs by a Type I IFN independent mechanism. IL-27 has previously been reported to inhibit HIV-1 replication in CD4+ T cells and macrophages, thus taken together, this cytokine is a potent anti-HIV agent against all major cell types targeted by the HIV-1 virus and may have a therapeutic role in the future.