title: Activation of TLR3/interferon signaling pathway by bluetongue virus results in HIV inhibition in macrophages.
abstract: Bluetongue virus (BTV), a nonenveloped double-stranded RNA virus, is a potent inducer of type Ι interferons in multiple cell systems. In this study, we report that BTV16 treatment of primary human macrophages induced both type I and III IFN expression, resulting in the production of multiple antiviral factors, including myxovirus resistance protein A, 2',5'-oligoadenylate synthetase, and the IFN-stimulated gene 56. Additionally, BTV-treated macrophages expressed increased HIV restriction factors (apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3 G/F/H) and CC chemokines (macrophage inflammatory protein 1-α, macrophage inflammatory protein 1-β, regulated on activation of normal T cell expressed and secreted), the ligands for HIV entry coreceptor CC chemokine receptor type 5. BTV16 also induced the expression of tetherin, which restricts HIV release from infected cells. Furthermore, TLR3 signaling of macrophages by BTV16 resulted in the induction of several anti-HIV microRNAs (miRNA-28, -29a, -125b, -150, -223, and -382). More importantly, the induction of antiviral responses by BTV resulted in significant suppression of HIV in macrophages. These findings demonstrate the potential of BTV-mediated TLR3 activation in macrophage innate immunity against HIV.
authors: *The Center for Animal Experiment/Animal Biological Safety Level 3 Laboratory, State Key Laboratory of Virology, Wuhan University, Wuhan, China, and Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Ming
authors: M
authors: Dai
authors: *The Center for Animal Experiment/Animal Biological Safety Level 3 Laboratory, State Key Laboratory of Virology, Wuhan University, Wuhan, China, and Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Xu
authors: X
authors: Wang
authors: *The Center for Animal Experiment/Animal Biological Safety Level 3 Laboratory, State Key Laboratory of Virology, Wuhan University, Wuhan, China, and Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Jie-Liang
authors: JL
authors: Li
authors: *The Center for Animal Experiment/Animal Biological Safety Level 3 Laboratory, State Key Laboratory of Virology, Wuhan University, Wuhan, China, and Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Yu
authors: Y
authors: Zhou
authors: *The Center for Animal Experiment/Animal Biological Safety Level 3 Laboratory, State Key Laboratory of Virology, Wuhan University, Wuhan, China, and Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Ming
authors: M
authors: Sang
authors: *The Center for Animal Experiment/Animal Biological Safety Level 3 Laboratory, State Key Laboratory of Virology, Wuhan University, Wuhan, China, and Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Jin-Biao
authors: JB
authors: Liu
authors: *The Center for Animal Experiment/Animal Biological Safety Level 3 Laboratory, State Key Laboratory of Virology, Wuhan University, Wuhan, China, and Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Jian-Guo
authors: JG
authors: Wu
authors: *The Center for Animal Experiment/Animal Biological Safety Level 3 Laboratory, State Key Laboratory of Virology, Wuhan University, Wuhan, China, and Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA wenzheho@temple.edu.
authors: Wen-Zhe
authors: WZ
authors: Ho
mesh_terms: D015703:Antigens, CD / Q000235:genetics; D001820:Bluetongue virus / Q000502:physiology*; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics; D058851:GPI-Linked Proteins / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D006678:HIV / Q000472:pathogenicity*; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D018925:Chemokines; D058851:GPI-Linked Proteins; D007372:Interferons; D051196:Toll-Like Receptor 3; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C495344:TLR3 protein, human
keywords: BTV; IFN-λ; UV-inactivated BTV; microRNA