title: RIG-I detects HIV-1 infection and mediates type I interferon response in human macrophages from patients with HIV-1-associated neurocognitive disorders.
abstract: The aim of this study was to explore the precise role of retinoic acid-inducible gene-I (RIG-I) signaling in human immunodeficiency virus type 1 (HIV-1)-infected macrophages from patients with HIV-1-associated neurocognitive disorders (HAND). Postmortem brain tissues were collected from patients with HIV-1-associated dementia and were compared to samples collected from HIV serum-positive patients without dementia and HIV serum-negative patients. A human monocyte-derived macrophage (MDM) primary culture system was established to evaluate the expression of RIG-I in these samples. Knockdown of RIG-I pathways genes was employed and STAT1 expression and phosphorylation levels were examined to explore the molecular mechanisms of HAND. The expression of RIG-I in postmortem brain tissue from HAND patients was significantly higher than in patients who were HIV serum-positive without dementia or HIV serum-negative. Moreover, we demonstrated that HIV-1 infection could result in a significant increase in the level of RIG-I in human MDMs. Moreover, a correlation was found between the increase in RIG-I expression and STAT1 expression and phosphorylation. Accordingly, knockdown of RIG-I decreased the phosphorylation of STAT1 and downregulated interferon-related genes. These observations highlight the importance of RIG-I signaling in anti-HIV innate immunity in macrophages, which may be beneficial for the treatment of HIV and aid in the understanding of the neuropathogenesis of HAND.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: M Q
authors.initials: MQ
authors.lastname: Wang
authors.affiliation: Laboratory of Neuroimmunology and Regenerative Therapy, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Y L
authors.initials: YL
authors.lastname: Huang
authors.affiliation: Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.affiliation: Laboratory of Neuroimmunology and Regenerative Therapy, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Zheng
authors.affiliation: Department of Biochemistry and Molecular Biology, ShanghaiJiao Tong University School of Medicine, Shanghai, China qinxianju@126.com.
authors.forename: G X
authors.initials: GX
authors.lastname: Qian
mesh_terms: D001921:Brain / Q000378:metabolism; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D015658:HIV Infections / Q000150:complications* / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D015497:HIV-1; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D000072640:Interferon-Induced Helicase, IFIH1; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D019965:Neurocognitive Disorders / Q000209:etiology* / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014779:Virus Replication
chemical_list: D007370:Interferon Type I; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D050794:STAT1 Transcription Factor; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1