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.
From the aLaboratory of Human Retrovirology, National Cancer Institute at Frederick, Frederick, Maryland, USA
bLaboratory of Immunopathogenesis and Bioinformatics, National Cancer Institute at Frederick, Frederick, Maryland, USA
cAIDS Monitoring Laboratory, National Cancer Institute at Frederick, Frederick, Maryland, USA
dClinical Services Program, Applied and Developmental Research Support Program, Science Application International Corporation (SAIC)-Frederick, Inc., National Cancer Institute at Frederick, Frederick, Maryland, USA
eLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda, Maryland, USA.
Received 20 June, 2007
Revised 4 October, 2007
Accepted 9 October, 2007
Correspondence to Tomozumi Imamichi, Building 550, Room 126, SAIC-Frederick, Inc., NCI-Frederick, PO Box B, Frederick, MD 21702-1201, USA. Tel: +1 301 846 5450; fax: +1 301 846 6762; e-mail: email@example.com