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AIDS:
doi: 10.1097/QAD.0b013e3282f3356c
Basic Science: Concise Communication

IL-27, a novel anti-HIV cytokine, activates multiple interferon-inducible genes in macrophages

Imamichi, Tomozumia,d; Yang, Junb,d; Huang, Da-Weib,d; Brann, Terrence Wa,d; Fullmer, Brandie Ab,d; Adelsberger, Joseph Wc,d; Lempicki, Richard Ab,d; Baseler, Michael Wd; Lane, H Clifforde

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Abstract

Objective: IL-27 is a novel anti-HIV cytokine that inhibits HIV-1 replication in both CD4 T cells and monocyte-derived macrophages (MDM) as IFN-α does. To elucidate the mechanism of the antiviral activity, we compared the activity and the gene expression profile of IL-27-treated cells with that of IFN-α-treated cells.

Methods: CD4 T cells and monocytes were isolated from peripheral blood mononuclear cells of healthy donors. CD4 T cells were stimulated with phytohemagglutinin, and MDM were induced from monocytes using macrophage-colony stimulating factor. HIV-1 replication was monitored by p24 antigen capture assay. The gene expression profiles were analysed using DNA microarray analysis. The increase in the expression of IFN-inducible genes (IFIG) was confirmed by the Quantigene plex assay.

Results: Both cytokines preferentially inhibited HIV-1 replication in MDM compared with CD4 T cells. Quantitative real time polymerase chain reaction, enzyme-linked immunosorbent assay and neutralization assay using anti-IFN indicated that IFN-α, IFN-β and IFN-γ had no significant impact on IL-27-mediated HIV inhibition. DNA microarray analysis illustrated that IFN-α induced 33 and 18 IFIG in MDM and CD4 T cells, respectively. IL-27 induced 28 IFIG in MDM and five IFIG in CD4 T cells. The quantitative assay confirmed that IL-27 activated genes of RNA-dependent kinase, oligoadenylate synthetase, myxovirus protein, and apolipoprotein B messenger RNA-editing enzyme-catalytic polypeptide-like 3G.

Conclusion: IL-27 differentially regulates the gene expression between CD4 T cells and MDM. IL-27 significantly induces antiviral genes in MDM as does IFN-α, suggesting that IL-27 inhibits HIV replication in MDM via mechanism(s) similar to that of IFN-α.

© 2008 Lippincott Williams & Wilkins, Inc.

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