title: HIV-1 infection induces acetylation of NPM1 that facilitates Tat localization and enhances viral transactivation.
abstract: Human immunodeficiency virus type 1 (HIV-1) following integration hijacks host cell machineries where chromatinization of the viral genome regulates its latency, transcription, and replication. The cooperation among ATP-dependent chromatin remodeling factors, posttranslational modifying enzymes, and histone chaperones is well established during transcriptional activation in eukaryotes. However, the role of histone chaperones in transcription of the HIV promoter is poorly understood. Previous studies from our group have established the role of the human histone chaperone nucleophosmin (NPM1) in the acetylation-dependent chromatin transcription. NPM1 is known to interact with HIV-Tat. Here, we report that infection by HIV-1 induces the acetylation of histone chaperone NPM1. Acetylation of NPM1 was found to be critical for nuclear localization of Tat as well as Tat-mediated transcription alluding to the critical role for the host factor towards viral pathogenesis. Furthermore, knockdown experiments mediated by small interfering RNA identified the critical role played by the chaperone NPM1 in transcriptional activation of the integrated provirus. These results shed further insights into the possible role of histone chaperone NPM1 acetylation in viral gene transcription, which could be a potential therapeutic target.
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore, India.
authors.forename: Shrikanth S
authors.initials: SS
authors.lastname: Gadad
authors.forename: Roshan Elizabeth
authors.initials: RE
authors.lastname: Rajan
authors.forename: Parijat
authors.initials: P
authors.lastname: Senapati
authors.forename: Snehajyoti
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Jayasha
authors.initials: J
authors.lastname: Shandilya
authors.forename: Prasanta Kumar
authors.initials: PK
authors.lastname: Dash
authors.forename: Udaykumar
authors.initials: U
authors.lastname: Ranga
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Kundu
mesh_terms: D000107:Acetylation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D020868:Gene Silencing; D015658:HIV Infections / Q000378:metabolism*; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D000090243:Nucleophosmin; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D021381:Protein Transport; D015533:Transcriptional Activation / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D000090243:Nucleophosmin