RRC ID 53152
Author Matsuda Y, Kobayashi-Ishihara M, Fujikawa D, Ishida T, Watanabe T, Yamagishi M.
Title Epigenetic heterogeneity in HIV-1 latency establishment.
Journal Sci Rep
Abstract Despite prolonged antiretroviral therapy, HIV-1 persists as transcriptionally inactive proviruses. The HIV-1 latency remains a principal obstacle in curing AIDS. It is important to understand mechanisms by which HIV-1 latency is established to make the latent reservoir smaller. We present a molecular characterization of distinct populations at an early phase of infection. We developed an original dual-color reporter virus to monitor LTR kinetics from establishment to maintenance stage. We found that there are two ways of latency establishment i.e., by immediate silencing and slow inactivation from active infection. Histone covalent modifications, particularly polycomb repressive complex 2 (PRC2)-mediated H3K27 trimethylation, appeared to dominate viral transcription at the early phase. PRC2 also contributes to time-dependent LTR dormancy in the chronic phase of the infection. Significant differences in sensitivity against several stimuli were observed between these two distinct populations. These results will expand our understanding of heterogeneous establishment of HIV-1 latency populations.
Volume 5
Pages 7701
Published 2015-1-9
DOI 10.1038/srep07701
PII srep07701
PMID 25572573
PMC PMC4287722
MeSH Chromatin Immunoprecipitation Epigenesis, Genetic* Genes, Reporter HEK293 Cells HIV-1 / genetics HIV-1 / physiology* Histones / metabolism Humans Jurkat Cells Methylation Polycomb Repressive Complex 2 / antagonists & inhibitors Polycomb Repressive Complex 2 / genetics Polycomb Repressive Complex 2 / metabolism RNA Interference RNA, Small Interfering / metabolism Virus Latency / genetics*
IF 3.998
Times Cited 35
DNA material CSII-EF-MCS-IRES2-Venus (RDB04384) CS-RfA-EF-mRFP1 (RDB05736) pENTR4-H1 (RDB04395) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394).