title: IFI44 suppresses HIV-1 LTR promoter activity and facilitates its latency.
abstract: IFI44 is an interferon-alfa inducible protein, and is associated with infection of several viruses. However, IFI44 elicits minimal antiviral effects on these viruses, and its exact role is still unknown. Here we show that IFI44 inhibits HIV-1 replication in vitro. Through depletion of endogenous IFI44 or overexpression of IFI44 we confirm that IFI44 suppresses HIV-1 LTR promoter activity and affects viral transcription. Furthermore, we find that IFI44 localizes to nuclei and binds to the HIV-1 LTR promoter in HIV-1 infected cells. Removing suppression of HIV-1 transcription benefits reactivation of HIV-1 proviruses for purging latent reservoirs. We demonstrate that depletion of endogenous IFI44 in J-LAT cells induces reactivation of latent HIV-1. Based on these results, we propose a model in which IFI44 is recruited to the HIV-1 LTR, which may suppress viral transcription and prevent reactivation of latent HIV-1. Our study suggests a previously unrecognized anti-HIV phenomenon for interferon-stimulated proteins.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Power
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA; Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Netty
authors.initials: N
authors.lastname: Santoso
authors.affiliation: School of Arts and Sciences, University of Rochester, Rochester, NY 14627, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Dieringer
authors.affiliation: School of Arts and Sciences, University of Rochester, Rochester, NY 14627, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Huachao
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Sydney
authors.initials: S
authors.lastname: Simpson
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Ishir
authors.initials: I
authors.lastname: Seth
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Miao
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA. Electronic address: Jian_Zhu@urmc.rochester.edu.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000941:Antigens / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000821:virology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D021381:Protein Transport; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D000941:Antigens; D003598:Cytoskeletal Proteins; C065888:IFI44 protein, human
keywords: HIV-1; IFI44; ISG; Interferon; LTR; Latency; Reactivation; Transcription