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

Abstract

Retinoblastoma binding protein4(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 type1(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) analysisrevealed that RbAp48 binds to the HIV-1 LTR invitro. Taken together, these findings demonstrate that, as a transcriptional cofactor, RbAp48 is likely to act as a potent antiretroviral defense.