| 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
|
| Resource |
| 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). |
