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HIV-1 Infection Induces Acetylation of NPM1 That Facilitates Tat Localization and Enhances Viral Transactivation
Journal article   Peer reviewed

HIV-1 Infection Induces Acetylation of NPM1 That Facilitates Tat Localization and Enhances Viral Transactivation

Shrikanth S. Gadad, Roshan Elizabeth Rajan, Parijat Senapati, Snehajyoti Chatterjee, Jayasha Shandilya, Prasanta Kumar Dash, Udaykumar Ranga and Tapas K. Kundu
Journal of molecular biology, Vol.410(5), pp.997-1007
07/29/2011
DOI: 10.1016/j.jmb.2011.04.009
PMID: 21763502

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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. (C) 2011 Elsevier Ltd. All rights reserved.
Biochemistry & Molecular Biology Life Sciences & Biomedicine Science & Technology

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