title: Epigenetic heterogeneity in HIV-1 latency establishment.
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.
authors.affiliation: Laboratory of Tumor Cell Biology, Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Matsuda
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Kobayashi-Ishihara
authors.affiliation: Laboratory of Tumor Cell Biology, Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Fujikawa
authors.affiliation: Research Center for Asian Infectious Disease, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Takaomi
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Laboratory of Tumor Cell Biology, Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Laboratory of Tumor Cell Biology, Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamagishi
mesh_terms: D047369:Chromatin Immunoprecipitation; D044127:Epigenesis, Genetic; D017930:Genes, Reporter; D057809:HEK293 Cells; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008745:Methylation; D063151:Polycomb Repressive Complex 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017735:Virus Latency / Q000235:genetics*
chemical_list: D006657:Histones; D034741:RNA, Small Interfering; D063151:Polycomb Repressive Complex 2