RbAp48, a novel inhibitory factor that regulates the transcription of human immunodeficiency virus type 1

Wang,Juan; Yang,Jin; Yang,Zongxing; Lu,Xiangyun; Jin,Changzhong; Cheng,Linfang; Wu,Nanping

doi:10.3892/ijmm.2016.2598

RbAp48, a novel inhibitory factor that regulates the transcription of human immunodeficiency virus type 1

Authors:
- Juan Wang
- Jin Yang
- Zongxing Yang
- Xiangyun Lu
- Changzhong Jin
- Linfang Cheng
- Nanping Wu
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Affiliations: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Afﬁliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China , Department of Medicine, Blood Center of Zhejiang Province, Hangzhou, Zhejiang 330100, P.R. China, Xixi Hospital of Hangzhou, Hangzhou, Zhejiang 310023, P.R. China
Published online on: May 19, 2016 https://doi.org/10.3892/ijmm.2016.2598
Pages: 267-274

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Abstract

Retinoblastoma binding protein 4 (RbAp48) is a histone chaperone which has been suggested to play a role in gene silencing. However, the role of RbAp48 in human immunodeficiency virus type 1 (HIV-1) infection and gene replication has not been determined to date, to the best of our knowledge. For this purpose, we demonstrated in the present study that RbAp48 expression was upregulated by HIV-1 infection, whereas the knockdown of RbAp48 promoted HIV infection and the production of virus particles. The ectopic expression of RbAp48 inhibited HIV-1 expression, and this inhibition correlated with a marked decrease in the expression of HIV-1 genomic RNA and various RNA transcripts. Further experiments to determine the mechanism responsible for the inhibitory effects of RbAp48 revealed that the ectopic expression of RbAp48 repressed HIV-1 long terminal repeat (LTR)-mediated basal transcription as well as TNF-α- and phorbol 12-myristate 13-acetate (PMA)‑activated transcription. Furthermore, the results of the electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) analysis revealed that RbAp48 binds to the HIV-1 LTR in vitro. Taken together, these findings demonstrate that, as a transcriptional cofactor, RbAp48 is likely to act as a potent antiretroviral defense.

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