title: A critical function of toll-like receptor-3 in the induction of anti-human immunodeficiency virus activities in macrophages.
abstract: Toll-like receptor-3 (TLR-3) recognizes double-stranded RNA and induces multiple intracellular events responsible for innate anti-viral immunity against a number of viral infections. Activation of TLR-3 inhibits human immunodeficiency virus (HIV) replication, but the mechanism(s) underlying the action of TLR-3 activation on HIV are largely unknown. Here we demonstrate that treatment of monocyte-derived macrophages with poly I:C, a synthetic ligand for TLR-3, significantly inhibited HIV infection and replication. Investigation of the mechanisms showed that TLR-3 activation resulted in the induction of type I interferon inducible antiviral factors, including APOBEC3G and tetherin, the newly identified anti-HIV cellular proteins. In addition, poly I:C-treated macrophages expressed increased levels of CC chemokines, the ligands for CCR5. Furthermore, TLR-3 activation in macrophages induced the expression of cellular microRNAs (miRNA-28, -125b, -150, -223 and -382), the newly identified intracellular HIV restriction factors. These findings indicate that TLR-3-mediated induction of multiple anti-HIV factors should be beneficial for the treatment of HIV disease where innate immune responses are compromised by the virus.
authors.affiliation: Division of Virology, Wuhan Centres for Disease Control and Prevention, Wuhan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Manqing
authors.initials: M
authors.lastname: Liu
authors.forename: Quan
authors.initials: Q
authors.lastname: Hu
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.forename: Dunjin
authors.initials: D
authors.lastname: Zhou
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Ho
mesh_terms: D000071480:APOBEC-3G Deaminase; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000998:Antiviral Agents / Q000276:immunology / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism; D058851:GPI-Linked Proteins; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D011070:Poly I-C / Q000378:metabolism / Q000494:pharmacology*; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000276:immunology / Q000378:metabolism*; D014779:Virus Replication / Q000276:immunology; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D000071480:APOBEC-3G Deaminase; D015703:Antigens, CD; D000998:Antiviral Agents; D019742:Chemokines, CC; D003564:Cytidine Deaminase; D058851:GPI-Linked Proteins; D007370:Interferon Type I; D008562:Membrane Glycoproteins; D035683:MicroRNAs; D011070:Poly I-C; D012330:RNA, Double-Stranded; D051196:Toll-Like Receptor 3; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C495344:TLR3 protein, human; C464924:APOBEC3G protein, human