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KSHV episome tethering sites on host chromosomes and regulation of latency-lytic switch by CHD4

  1. Author:
    Kumar, Ashish
    Lyu, Yuanzhi
    Yanagihashi, Yuichi
    Chantarasrivong, Chanikarn
    Majerciak,Vladimir
    Salemi, Michelle
    Wang, Kang-Hsin
    Inagaki, Tomoki
    Chuang, Frank
    Davis, Ryan R
    Tepper, Clifford G
    Nakano, Kazushi
    Izumiya, Chie
    Shimoda, Michiko
    Nakajima, Ken-Ichi
    Merleev, Alexander
    Zheng, Zhi-Ming
    Campbell, Mel
    Izumiya, Yoshihiro

  2. Author Address

    Department of Dermatology School of Medicine, University of California Davis (UC Davis), Sacramento, CA 95817, USA., Lifescience Division, Lifematics, Osaka, Osaka 541-0046, Japan., Tumor Virus RNA Biology Section, HIV Dynamics and Replication Program, National Cancer Institute, NIH, Frederick, MD 21702, USA., Genome Center, Proteomics Core, Genome and Biomedical Sciences Facility, UC Davis, Davis, CA 95616, USA., Department of Biochemistry and Molecular Medicine, School of Medicine, UC Davis, Sacramento, CA 95817, USA., Department of Pathology and Laboratory Medicine, School of Medicine, UC Davis, Sacramento, CA 95817, USA., Department of Biochemistry and Molecular Medicine, School of Medicine, UC Davis, Sacramento, CA 95817, USA; Viral Oncology and Pathogen-Associated Malignancies Initiative, UC Davis Comprehensive Cancer Center, Sacramento, CA 95817, USA., Department of Dermatology School of Medicine, University of California Davis (UC Davis), Sacramento, CA 95817, USA; Viral Oncology and Pathogen-Associated Malignancies Initiative, UC Davis Comprehensive Cancer Center, Sacramento, CA 95817, USA., Department of Dermatology School of Medicine, University of California Davis (UC Davis), Sacramento, CA 95817, USA. Electronic address: mcampbell@ucdavis.edu., Department of Dermatology School of Medicine, University of California Davis (UC Davis), Sacramento, CA 95817, USA; Department of Biochemistry and Molecular Medicine, School of Medicine, UC Davis, Sacramento, CA 95817, USA; Viral Oncology and Pathogen-Associated Malignancies Initiative, UC Davis Comprehensive Cancer Center, Sacramento, CA 95817, USA. Electronic address: yizumiya@ucdavis.edu.,
    1. Year: 2022
    2. Date: May 10
  2. Journal: Cell Reports
    1. 39
    2. 6
    3. Pages: 110788
  4. Type of Article: Article
  5. Article Number: 110788
  1. Abstract:

    Kaposi sarcoma-associated herpesvirus (KSHV) establishes a latent infection in the cell nucleus, but where KSHV episomal genomes are tethered and the mechanisms underlying KSHV lytic reactivation are unclear. Here, we study the nuclear microenvironment of KSHV episomes and show that the KSHV latency-lytic replication switch is regulated via viral long non-coding (lnc)RNA-CHD4 (chromodomain helicase DNA binding protein 4) interaction. KSHV episomes localize with CHD4 and ADNP proteins, components of the cellular ChAHP complex. The CHD4 and ADNP proteins occupy the 5'-region of the highly inducible lncRNAs and terminal repeats of the KSHV genome together with latency-associated nuclear antigen (LANA). Viral lncRNA binding competes with CHD4 DNA binding, and KSHV reactivation sequesters CHD4 from the KSHV genome, which is also accompanied by detachment of KSHV episomes from host chromosome docking sites. We propose a model in which robust KSHV lncRNA expression determines the latency-lytic decision by regulating LANA/CHD4 binding to KSHV episomes. Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

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External Sources

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  2. DOI: 10.1016/j.celrep.2022.110788
  3. PMID: 35545047
  4. PII : S2211-1247(22)00555-1

Library Notes

  1. Fiscal Year: FY2021-2022
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