Journal Article

IFN-λ3 Inhibits HIV Infection of Macrophages through the JAK-STAT Pathway

Zhou, Wang, Ho, Wen-Zhe, Liu, Man-Qing, Wang, Xu, Wang, Yi-Zhong, Zhou, Dun-Jin, Li, Jie-Liang, Ye, Li

2012

Overview

Interferon lambda 3 (IFN-λ3) is a newly identified cytokine with antiviral activity, and its single nucleotide polymorphisms are strongly associated with the treatment effectiveness and development of chronic hepatitis C virus infection. We thus examined the potential of IFN-λ3 to inhibit HIV replication and the possible mechanisms of the anti-HIV action by IFN-λ3 in human macrophages. Under different conditions (before, during, and after HIV infection), IFN-λ3 significantly inhibited viral replication in macrophages, which was associated with the induction of multiple antiviral cellular factors (ISG56, MxA, OAS-1, A3G/F and tetherin) and IFN regulatory factors (IRF-1, 3, 5, 7 and 9). This anti-HIV action of IFN-λ3 could be compromised by the JAK-STAT inhibitor. In addition, IFN-λ3 treatment of macrophages induced the expression of toll-like receptor 3 (TLR3) and two key adaptors (MyD88 and TRIF) in type I IFN pathway activation. However, HIV infection compromised IFN-λ3-mediated induction of the key elements in JAK-STAT signaling pathway. These data indicate that IFN-λ3 exerts its anti-HIV function by activating JAK-STAT pathway-mediated innate immunity in macrophages. Future in vivo studies are necessary in order to explore the potential for developing IFN-λ3-based therapy for HIV disease.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adapters / Adaptor proteins / Adaptor Proteins, Vesicular Transport - genetics / Adaptor Proteins, Vesicular Transport - immunology / Antigens, Differentiation, B-Lymphocyte - genetics / Antigens, Differentiation, B-Lymphocyte - immunology / Antiviral activity / Biology / Cells, Cultured / Chronic infection / Disease prevention / Gene Expression Regulation - drug effects / Hepatitis / Hepatitis C / HIV / HIV-1 - drug effects / HIV-1 - physiology / Human immunodeficiency virus / Humans / Immunity / Immunity, Innate / In vivo methods and tests / Innate immunity / Interferon / Interferon regulatory factor 1 / Interferon Regulatory Factors - genetics / Interferon Regulatory Factors - immunology / Interferons / Interleukins - immunology / Interleukins - pharmacology / Janus Kinases - antagonists & inhibitors / Janus Kinases - genetics / Janus Kinases - immunology / Macrophages / Macrophages - drug effects / Macrophages - immunology / Macrophages - virology / Medicine / Membrane Glycoproteins - genetics / Membrane Glycoproteins - immunology / MyD88 protein / Phosphorylation / Protein Kinase Inhibitors - pharmacology / Receptors, Interleukin-1 - genetics / Receptors, Interleukin-1 - immunology / Replication / Signal transduction / Signal Transduction - drug effects / Signaling / Single-nucleotide polymorphism / STAT Transcription Factors - genetics / STAT Transcription Factors - immunology / TLR3 protein / Toll-Like Receptor 3 - genetics / Toll-Like Receptor 3 - immunology / Toll-like receptors / Viral infections / Virus Replication - drug effects / Viruses