title: Epigenetic Landscape of Kaposi's Sarcoma-Associated Herpesvirus Genome in Classic Kaposi's Sarcoma Tissues.
abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically related to Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). It typically displays two different phases in its life cycle, the default latency and occasional lytic replication. The epigenetic modifications are thought to determine the fate of KSHV infection. Previous studies elegantly depicted epigenetic landscape of latent viral genome in in vitro cell culture systems. However, the physiologically relevant scenario in clinical KS tissue samples is unclear. In the present study, we established a protocol of ChIP-Seq for clinical KS tissue samples and mapped out the epigenetic landscape of KSHV genome in classic KS tissues. We examined AcH3 and H3K27me3 histone modifications on KSHV genome, as well as the genome-wide binding sites of latency associated nuclear antigen (LANA). Our results demonstrated that the enriched AcH3 was mainly restricted at latent locus while H3K27me3 was widespread on KSHV genome in classic KS tissues. The epigenetic landscape at the region of vIRF3 gene confirmed its silenced state in KS tissues. Meanwhile, the abundant enrichment of LANA at the terminal repeat (TR) region was also validated in the classic KS tissues, however, different LANA binding sites were observed on the host genome. Furthermore, we verified the histone modifications by ChIP-qPCR and found the dominant repressive H3K27me3 at the promoter region of replication and transcription activator (RTA) in classic KS tissues. Intriguingly, we found that the TR region in classic KS tissues was lacking in AcH3 histone modifications. These data now established the epigenetic landscape of KSHV genome in classic KS tissues, which provides new insights for understanding KSHV epigenetics and pathogenesis.
authors.affiliation: CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.affiliation: School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Tan
authors.affiliation: CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.affiliation: First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Otorhinolaryngology and Tumor Virology Program, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Erle S
authors.initials: ES
authors.lastname: Robertson
authors.affiliation: State Key Laboratory of Virology, College of Life Science, Wuhan University, Wuhan, Hubei, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Lan
mesh_terms: D000956:Antigens, Viral / Q000235:genetics; D002460:Cell Line; D044127:Epigenesis, Genetic; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral / Q000235:genetics*; D019288:Herpesvirus 8, Human / Q000235:genetics*; D042421:Histone Code; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012514:Sarcoma, Kaposi / Q000821:virology*; D012878:Skin Neoplasms / Q000821:virology*; D020079:Terminal Repeat Sequences / Q000235:genetics
chemical_list: D000956:Antigens, Viral; D009687:Nuclear Proteins; C109540:latency-associated nuclear antigen