title: RIG-I activation inhibits HIV replication in macrophages.
abstract: The RIG-I signaling pathway is critical in the activation of the type I IFN-dependent antiviral innate-immune response. We thus examined whether RIG-I activation can inhibit HIV replication in macrophages. We showed that the stimulation of monocyte-derived macrophages with 5'ppp-dsRNA, a synthetic ligand for RIG-I, induced the expression of RIG-I, IFN-α/β, and several IRFs, key regulators of the IFN signaling pathway. In addition, RIG-I activation induced the expression of multiple intracellular HIV-restriction factors, including ISGs, several members of the APOBEC3 family, tetherin and CC chemokines, the ligands for HIV entry coreceptor (CCR5). The inductions of these factors were associated with the inhibition of HIV replication in macrophages stimulated by 5'ppp-dsRNA. These observations highlight the importance of RIG-I signaling in macrophage innate immunity against HIV, which can be beneficial for the treatment of HIV disease, where intracellular immune defense is compromised by the virus.
authors.affiliation: Temple University School of Medicine, 843 MERB, 3500 N. Broad St., Philadelphia, PA 19140, USA. wenzheho@temple.edu
authors.forename: Yizhong
authors.initials: Y
authors.lastname: Wang
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Jieliang
authors.initials: J
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Ho
mesh_terms: D000071478:APOBEC Deaminases; D015703:Antigens, CD / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000502:physiology; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000502:physiology*; D058851:GPI-Linked Proteins / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D054303:HIV Reverse Transcriptase / Q000032:analysis; D015497:HIV-1 / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D016898:Interferon-alpha / Q000096:biosynthesis / Q000235:genetics; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics; D008024:Ligands; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000821:virology*; D009000:Monocytes / Q000166:cytology; D012330:RNA, Double-Stranded / Q000276:immunology; D012367:RNA, Viral / Q000276:immunology; D019713:Receptors, CCR5 / Q000502:physiology; D011971:Receptors, Immunologic; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D000071478:APOBEC Deaminases; D015703:Antigens, CD; D018925:Chemokines; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D058851:GPI-Linked Proteins; D054303:HIV Reverse Transcriptase; D016898:Interferon-alpha; D016899:Interferon-beta; D008024:Ligands; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D019713:Receptors, CCR5; D011971:Receptors, Immunologic; C551867:5'PPP-RNA; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514824:reverse transcriptase, Human immunodeficiency virus 1; C502889:APOBEC3 proteins, human; C452820:RIGI protein, human
keywords: APOBEC3; interferon regulatory factors; interferon-stimulated genes; type I interferon