title: Identification of HIV-1 Tat-Associated Proteins Contributing to HIV-1 Transcription and Latency.
abstract: Human immunodeficiency virus type 1 (HIV-1) Tat is a virus-encoded trans-activator that plays a central role in viral transcription. We used our recently developed parallel analysis of in vitro translated open reading frames (ORFs) (PLATO) approach to identify host proteins that associate with HIV-1 Tat. From this proteomic assay, we identify 89 Tat-associated proteins (TAPs). We combine our results with other datasets of Tat or long terminal repeat (LTR)-associated proteins. For some of these proteins (NAT10, TINP1, XRCC5, SIN3A), we confirm their strong association with Tat. These TAPs also suppress Tat-mediated HIV-1 transcription. Removing suppression of HIV-1 transcription benefits the reversal of post-integrated, latent HIV-1 proviruses. We demonstrate that these transcriptionally suppressing TAPs contribute to HIV-1 latency in Jurkat latency (J-LAT) cells. Therefore, our proteomic analysis highlights the previously unappreciated TAPs that play a role in maintaining HIV-1 latency and can be further studied as potential pharmacological targets for the "shock and kill" HIV-1 cure strategy.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA. Maxime_Jean@urmc.rochester.edu.
authors.forename: Maxime Junior
authors.initials: MJ
authors.lastname: Jean
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA. derekpow@buffalo.edu.
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. Weili_Kong@urmc.rochester.edu.
authors.forename: Weili
authors.initials: W
authors.lastname: Kong
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA. Huachao_Huang@urmc.rochester.edu.
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. Netty_Santoso@urmc.rochester.edu.
authors.forename: Netty
authors.initials: N
authors.lastname: Santoso
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA. Jian_Zhu@urmc.rochester.edu.|Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USA. Jian_Zhu@urmc.rochester.edu.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
mesh_terms: D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D019169:Jurkat Cells; D011485:Protein Binding; D020543:Proteome / Q000032:analysis; D014158:Transcription, Genetic; D017735:Virus Latency; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D020543:Proteome; D054322:tat Gene Products, Human Immunodeficiency Virus
keywords: HIV; PLATO; Tat; latency; protein interaction; proteomics; ribosome display; transcription