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J Virol. 2009 Apr;83(8):3834-42. doi: 10.1128/JVI.01773-08. Epub 2009 Feb 4.

Lambda interferon inhibits human immunodeficiency virus type 1 infection of macrophages.

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  • 1Division of Allergy & Immunology, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 34th Street & Civic Center Boulevard, Philadelphia, PA 19104, USA.

Abstract

The newly identified type III interferon (IFN-lambda) has antiviral activity against a broad spectrum of viruses. We thus examined whether IFN-lambda has the ability to inhibit human immunodeficiency virus type 1 (HIV-1) infection of blood monocyte-derived macrophages that expressed IFN-lambda receptors. Both IFN-lambda1 and IFN-lambda2, when added to macrophage cultures, inhibited HIV-1 infection and replication. This IFN-lambda-mediated anti-HIV-1 activity is broad, as IFN-lambda could inhibit infection by both laboratory-adapted and clinical strains of HIV-1. Investigations of the mechanism(s) responsible for the IFN-lambda action showed that although IFN-lambda had little effect on HIV-1 entry coreceptor CCR5 expression, IFN-lambda induced the expression of CC chemokines, the ligands for CCR5. In addition, IFN-lambda upregulated intracellular expression of type I IFNs and APOBEC3G/3F, the newly identified anti-HIV-1 cellular factors. These data provide direct and compelling evidence that IFN-lambda, through both extracellular and intracellular antiviral mechanisms, inhibits HIV-1 replication in macrophages. These findings indicate that IFN-lambda may have therapeutic value in the treatment of HIV-1 infection.

PMID:
19193806
[PubMed - indexed for MEDLINE]
PMCID:
PMC2663280
Free PMC Article
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