Lambda interferon inhibits human immunodeficiency virus type 1 infection of macrophages.
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.
Hou
Wei
W
Division of Allergy & Immunology, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 34th Street & Civic Center Boulevard, Philadelphia, PA 19104, USA.
Wang
Xu
X
Ye
Li
L
Zhou
Lin
L
Yang
Zhan-Qiu
ZQ
Riedel
Eric
E
Ho
Wen-Zhe
WZ
D000071480:APOBEC-3G Deaminase; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000096:biosynthesis; D003564:Cytidine Deaminase / Q000096:biosynthesis; D043525:Cytosine Deaminase / Q000096:biosynthesis; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis; D007372:Interferons; D007378:Interleukins / Q000276:immunology*; D008264:Macrophages / Q000821:virology*; D015854:Up-Regulation; D000095022:Interferon Lambda
D000071480:APOBEC-3G Deaminase; D019742:Chemokines, CC; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase; D007370:Interferon Type I; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C492906:APOBEC3F protein, human; C464924:APOBEC3G protein, human