AIDS

Skip Navigation LinksHome > January 2, 2008 - Volume 22 - Issue 1 > IL-27, a novel anti-HIV cytokine, activates multiple interfe...
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

Collapse Box

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.

Login

Article Tools

Share

Article Level Metrics

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.