title: MicroRNA-155 Reinforces HIV Latency.
abstract: The presence of a small number of infected but transcriptionally dormant cells currently thwarts a cure for the more than 35 million individuals infected with HIV. Reactivation of these latently infected cells may result in three fates: 1) cell death due to a viral cytopathic effect, 2) cell death due to immune clearance, or 3) a retreat into latency. Uncovering the dynamics of HIV gene expression and silencing in the latent reservoir will be crucial for developing an HIV-1 cure. Here we identify and characterize an intracellular circuit involving TRIM32, an HIV activator, and miR-155, a microRNA that may promote a return to latency in these transiently activated reservoir cells. Notably, we demonstrate that TRIM32, an E3 ubiquitin ligase, promotes reactivation from latency by directly modifying IκBα, leading to a novel mechanism of NF-κB induction not involving IκB kinase activation.
authors: From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158, the Biomedical Sciences Program and.
authors: Debbie S
authors: DS
authors: Ruelas
authors: From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158.
authors: Jonathan K
authors: JK
authors: Chan
authors: the Department of Molecular and Cell Biology and.
authors: Eugene
authors: E
authors: Oh
authors: the Biomedical Sciences Program and the Gladstone Institute of Cardiovascular Disease, San Francisco, California 94158.
authors: Amy J
authors: AJ
authors: Heidersbach
authors: From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158.
authors: Andrew M
authors: AM
authors: Hebbeler
authors: From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158, the Biomedical Sciences Program and.
authors: Leonard
authors: L
authors: Chavez
authors: From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158, the Departments of Medicine and Microbiology and Immunology, University of California, San Francisco, California 94143.
authors: Eric
authors: E
authors: Verdin
authors: the Department of Molecular and Cell Biology and the Howard Hughes Medical Institute, University of California, Berkeley, California 94720, and.
authors: Michael
authors: M
authors: Rape
authors: From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158, the Departments of Medicine and Microbiology and Immunology, University of California, San Francisco, California 94143, wgreene@gladstone.ucsf.edu.
authors: Warner C
authors: WC
authors: Greene
mesh_terms: D020413:3' Untranslated Regions; D020816:Amino Acid Motifs; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D016923:Cell Death; D020868:Gene Silencing; D017930:Genes, Reporter; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016086:Lentivirus / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism*; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin / Q000737:chemistry; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D020413:3' Untranslated Regions; D020672:I-kappa B Proteins; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin; D000072000:NF-KappaB Inhibitor alpha; C084523:TRIM25 protein, human; C094027:TRIM32 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: HIV-1 latency; IκBα; NF-kappa B (NF-KB); TRIM32; microRNA (miRNA); molecular biology; viral transcription; virology