Genome-wide analysis of histone modifications in latently HIV-1 infected T cells

Abstract

Objectives:The transcriptional silencing of HIV type 1 (HIV-1) provirus in latently infected cells is a major hurdle on the pathway to HIV-1 elimination. The epigenetic mechanisms established by histone modifications may affect the transcriptional silencing of HIV-1 and viral latency. A systematic epigenome profiling could be applicable to develop new epigenetic diagnostic markers for detecting HIV-1 latency.Design:The HIV-1 latency cell lines (NCHA1, NCHA2 and ACH2] were compared with CD4+ T-cell line (A3.01).Methods:The histone modification profiles obtained from chromatin immunoprecipiation followed by sequencing (ChIP-Seq) for histone H3K4me3 and H3K9ac were systematically examined and differential gene expression patterns along with levels of histone modifications were used for network analysis.Results:The HIV-1 latency gave rise to downregulation of histone H3K4me3 and H3K9ac levels in 387 and 493 regions and upregulation in 451 and 962 sites, respectively. By network analysis, five gene clusters were associated with downregulated histone modifications and six gene clusters came up with upregulated histone modifications. Integration of gene expression with epigenetic information revealed that the cell cycle regulatory genes such as CDKN1A (p21) and cyclin D2 (CCND2) identified by differentially modified histones might play an important role in maintaining the HIV-1 latency.Conclusion:The transcriptional regulation by epigenetic memory should play a key role in the evolution and maintenance of HIV-1 latency accompanied by modulation of signalling molecules in the host cells.

EZH2 phosphorylation regulates Tat‐induced HIV‐1 transactivation via ROS/Akt signaling pathway

“…Tat simultaneously decreases repressive histone methylation and increases histone acetylation at the proviral promoter. These histone modifications have been previously associated with transactivation of the HIV provirus in the promoter region [33–34]. Interestingly, we observed that EZH2 is increased in the cytoplasm after Tat treatment, which is unusual considering that EZH2 is predominantly a nuclear protein.…”

Geminivirus-encoded TrAP suppressor inhibits the histone methyltransferase SUVH4/KYP to counter host defense

“…In eukaryotes, chromatin appears to be a critical battleground for virus–host interaction. Animals use histone modifications to reinforce the latency of integrated viruses ( du Chene et al, 2007 ; Narasipura et al, 2014 ; Park et al, 2014 ). Plant DNA viruses including Geminiviruses and pararetroviruses replicate as nuclear minichromosomes or episomes.…”

Histone deacetylase inhibitors induce complex host responses that contribute to differential potencies of these compounds in HIV reactivation

“…Whereas this gene has been known to be modulated by HDACis and have a role in their anti-tumor properties (24,46), it was essentially not modulated at all in the in vitro model of HIV latency in the present study (Table S1). Because its expression was elevated in the cell line models of HIV latency, it was proposed as a latency biomarker (47). Its expression in elite controllers was higher, compared with progressors and HIV seronegative individuals; CDKN1A/p21 inhibited reverse transcription of the HIV genome and transcription from the integrated provirus via inhibition of cyclin-dependent kinase 9 (CDK9), a component of P-TEFb (48).…”