Epigenetic Heterogeneity in HIV-1 Latency Establishment

Yuka Matsuda, Mie Kobayashi-Ishihara, Dai Fujikawa, Takaomi Ishida, Toshiki Watanabe, Makoto Yamagishi

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish
Article number7701
JournalScientific reports
Volume5
DOIs
Publication statusPublished - 2015 Jan 9

ASJC Scopus subject areas

  • General

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    Matsuda, Y., Kobayashi-Ishihara, M., Fujikawa, D., Ishida, T., Watanabe, T., & Yamagishi, M. (2015). Epigenetic Heterogeneity in HIV-1 Latency Establishment. Scientific reports, 5, [7701]. https://doi.org/10.1038/srep07701