title: RbAp48, a novel inhibitory factor that regulates the transcription of human immunodeficiency virus type 1.
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.
authors.affiliation: 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.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Medicine, Blood Center of Zhejiang Province, Hangzhou, Zhejiang 330100, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Xixi Hospital of Hangzhou, Hangzhou, Zhejiang 310023, P.R. China.
authors.forename: Zongxing
authors.initials: Z
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Xiangyun
authors.initials: X
authors.lastname: Lu
authors.affiliation: 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.
authors.forename: Changzhong
authors.initials: C
authors.lastname: Jin
authors.affiliation: 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.
authors.forename: Linfang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: 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.
authors.forename: Nanping
authors.initials: N
authors.lastname: Wu
mesh_terms: D057809:HEK293 Cells; D015658:HIV Infections / Q000235:genetics / Q000821:virology; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D056505:Retinoblastoma-Binding Protein 4 / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D056505:Retinoblastoma-Binding Protein 4