Nuclear protein phosphatase-1 regulates HIV-1 transcription.
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.
Ammosova
Tatyana
T
Center for Sickle Cell Disease and Department of Biochemistry and Molecular Biology, Howard University, Washington, D. C. 20059, USA.
Jerebtsova
Marina
M
Beullens
Monique
M
Voloshin
Yaroslav
Y
Ray
Patricio E
PE
Kumar
Ajit
A
Bollen
Mathieu
M
Nekhai
Sergei
S
D002467:Cell Nucleus / Q000201:enzymology*; D000229:Dependovirus / Q000235:genetics; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000502:physiology*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D054645:Protein Phosphatase 1; D014158:Transcription, Genetic / Q000502:physiology*; D014779:Virus Replication
D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1