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    J Biol Chem. 2003 Aug 22;278(34):32189-94. Epub 2003 Jun 4.

    Nuclear protein phosphatase-1 regulates HIV-1 transcription.

    Ammosova T, Jerebtsova M, Beullens M, Voloshin Y, Ray PE, Kumar A, Bollen M, Nekhai S.

    Source

    Center for Sickle Cell Disease and Department of Biochemistry and Molecular Biology, Howard University, Washington, D. C. 20059, USA.

    Abstract

    We recently reported that protein phosphatase 1 (PP1) dephosphorylates RNA polymerase II C-terminal repeats and regulates HIV-1 transcription in vitro. Here we provide evidence that PP1 is also required for Tat-induced HIV-1 transcription and for viral replication in cultured cells. Inhibition of PP1 by overexpression of nuclear inhibitor of PP1 (NIPP1) inhibited Tat-induced HIV-1 transcription in transient transfection assays. A mutant of NIPP1 that was defective in binding to PP1 did not have this effect. Also the co-expression of PP1 gamma reversed the inhibitory effect of NIPP1. Adeno-associated virus-mediated delivery of NIPP1 significantly reduced HIV-1 transcription induced by Tat-expressing adenovirus in CD4+ HeLa cells that contained an integrated HIV-1 promoter (HeLa MAGI cells). In addition, infection of HeLa MAGI cells with adeno-associated virus-NIPP1 prior to the infection with HIV-1 significantly reduced the level of HIV-1 replication. Our results indicate that PP1 might be a host cell factor that is required for HIV-1 viral transcription. Therefore, nuclear PP1 may represent a novel target for anti-HIV-1 therapeutics.

    PMID:
    12788939
    [PubMed - indexed for MEDLINE]
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