title: IFN-λ3 inhibits HIV infection of macrophages through the JAK-STAT pathway.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Virology, Wuhan Center for Disease Prevention & Control, Wuhan, Hubei, People's Republic of China.
authors.forename: Man-Qing
authors.initials: MQ
authors.lastname: Liu
authors.forename: Dun-Jin
authors.initials: DJ
authors.lastname: Zhou
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Wang
authors.initials: W
authors.lastname: Zhou
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.forename: Jie-Liang
authors.initials: JL
authors.lastname: Li
authors.forename: Yi-Zhong
authors.initials: YZ
authors.lastname: Wang
authors.forename: Wen-Zhe
authors.initials: WZ
authors.lastname: Ho
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology; D007372:Interferons; D007378:Interleukins / Q000276:immunology / Q000494:pharmacology*; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000276:immunology; D050791:STAT Transcription Factors / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects*; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects; D000095022:Interferon Lambda
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000944:Antigens, Differentiation, B-Lymphocyte; D050835:Interferon Regulatory Factors; D007372:Interferons; D007378:Interleukins; D053612:Janus Kinases; D008562:Membrane Glycoproteins; D047428:Protein Kinase Inhibitors; D017472:Receptors, Interleukin-1; D050791:STAT Transcription Factors; D051196:Toll-Like Receptor 3; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C470409:TICAM1 protein, human; C434984:TIRAP protein, human; C495344:TLR3 protein, human