Role of retinoblastoma protein-associated protein 48 (RBBP4) in HIV-1 latency

Abstract

Objective To investigate the role and mechanism of retinoblastoma protein-associated proteins 48 (RBBP4) in HIV-1 latency. Methods CEM-Bru cells latently infected with HIV-1 were stimulated with 25 ng/ml of tumor necrosis factor alpha (TNF-α) in combination with 10 ng/ml of interleukin-2 (IL-2). Chromatin immunoprecipitation (ChIP) was performed to detect the changes in RBBP4 and in histone deacetylases 1 and 2 (HDAC1/2) binding to long terminal repeat (LTR). Binding activities of HDAC1/2 and RNA polymerase Ⅱ (RNA Pol Ⅱ) to LTR and acetylated histone H3 at LTR region were detected by ChIP after partially interfering the expression of RBBP4 in CEM-Bru cells with electroporation. Initiating and elongated transcripts were measured by RT-PCR. Results The binding activities of RBBP4 and HDAC1/2 to LTR in HIV-1 latently infected cells were enhanced significantly as compared with those in TNF-α and IL-2 co-stimulated cells. Fewer RBBP4 and HDAC1/2 bound to LTR following the interference of RBBP4 expression, which was accompanied with enhanced histone acetylation and strengthened binding activity of RNA Pol Ⅱ to LTR. Moreover, more initiating transcripts were detected in HIV-1 latently infected cells after the RBBP4 expression was interfered by electroporation. Conclusion RBBP4 contributes to the maintenance of HIV-1 latency, in which HDAC1 and HDAC2 might be involved. Key words: RBBP4; HDAC1; HDAC2; HIV-1; Latency