IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-51961-y.html
   My bibliography  Save this article

Human cytomegalovirus harnesses host L1 retrotransposon for efficient replication

Author

Listed:
  • Sung-Yeon Hwang

    (Institute for Basic Science
    Seoul National University
    Seoul National University)

  • Hyewon Kim

    (Institute for Basic Science
    Seoul National University
    Seoul National University)

  • Danielle Denisko

    (Boston Children’s Hospital and Harvard Medical School
    Harvard Medical School)

  • Boxun Zhao

    (Boston Children’s Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard
    Boston Children’s Hospital)

  • Dohoon Lee

    (Seoul National University
    Seoul National University)

  • Jiseok Jeong

    (Institute for Basic Science
    Seoul National University
    Seoul National University)

  • Jinuk Kim

    (Seoul National University)

  • Kiwon Park

    (Institute for Basic Science
    Seoul National University
    Seoul National University)

  • Junhyun Park

    (Institute for Basic Science
    Seoul National University
    Seoul National University)

  • Dongjoon Jeong

    (Institute for Basic Science
    Seoul National University
    Seoul National University)

  • Sehong Park

    (Institute for Basic Science
    Seoul National University
    Seoul National University)

  • Hee-Jung Choi

    (Seoul National University)

  • Sun Kim

    (Seoul National University)

  • Eunjung Alice Lee

    (Boston Children’s Hospital and Harvard Medical School
    Harvard Medical School
    Broad Institute of MIT and Harvard
    Boston Children’s Hospital)

  • Kwangseog Ahn

    (Institute for Basic Science
    Seoul National University
    Seoul National University)

Abstract

Genetic parasites, including viruses and transposons, exploit components from the host for their own replication. However, little is known about virus-transposon interactions within host cells. Here, we discover a strategy where human cytomegalovirus (HCMV) hijacks L1 retrotransposon encoded protein during its replication cycle. HCMV infection upregulates L1 expression by enhancing both the expression of L1-activating transcription factors, YY1 and RUNX3, and the chromatin accessibility of L1 promoter regions. Increased L1 expression, in turn, promotes HCMV replicative fitness. Affinity proteomics reveals UL44, HCMV DNA polymerase subunit, as the most abundant viral binding protein of the L1 ribonucleoprotein (RNP) complex. UL44 directly interacts with L1 ORF2p, inducing DNA damage responses in replicating HCMV compartments. While increased L1-induced mutagenesis is not observed in HCMV for genetic adaptation, the interplay between UL44 and ORF2p accelerates viral DNA replication by alleviating replication stress. Our findings shed light on how HCMV exploits host retrotransposons for enhanced viral fitness.

Suggested Citation

  • Sung-Yeon Hwang & Hyewon Kim & Danielle Denisko & Boxun Zhao & Dohoon Lee & Jiseok Jeong & Jinuk Kim & Kiwon Park & Junhyun Park & Dongjoon Jeong & Sehong Park & Hee-Jung Choi & Sun Kim & Eunjung Alic, 2024. "Human cytomegalovirus harnesses host L1 retrotransposon for efficient replication," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51961-y
    DOI: 10.1038/s41467-024-51961-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-51961-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-51961-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Nicole G. Coufal & José L. Garcia-Perez & Grace E. Peng & Gene W. Yeo & Yangling Mu & Michael T. Lovci & Maria Morell & K. Sue O’Shea & John V. Moran & Fred H. Gage, 2009. "L1 retrotransposition in human neural progenitor cells," Nature, Nature, vol. 460(7259), pages 1127-1131, August.
    2. Michael Grunstein, 1997. "Histone acetylation in chromatin structure and transcription," Nature, Nature, vol. 389(6649), pages 349-352, September.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Thomas B. Kepler & Timothy C. Elston, 2001. "Stochasticity in Transcriptional Regulation: Origins, Consequences and Mathematical Representations," Working Papers 01-06-033, Santa Fe Institute.
    2. Avinash B. Patel & Jinkang Qing & Kelly H. Tam & Sara Zaman & Maria Luiso & Ishwar Radhakrishnan & Yuan He, 2023. "Cryo-EM structure of the Saccharomyces cerevisiae Rpd3L histone deacetylase complex," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    3. Ahmad Luqman-Fatah & Yuzo Watanabe & Kazuko Uno & Fuyuki Ishikawa & John V. Moran & Tomoichiro Miyoshi, 2023. "The interferon stimulated gene-encoded protein HELZ2 inhibits human LINE-1 retrotransposition and LINE-1 RNA-mediated type I interferon induction," Nature Communications, Nature, vol. 14(1), pages 1-26, December.
    4. Chen Sun & Kunal Kathuria & Sarah B. Emery & ByungJun Kim & Ian E. Burbulis & Joo Heon Shin & Daniel R. Weinberger & John V. Moran & Jeffrey M. Kidd & Ryan E. Mills & Michael J. McConnell, 2024. "Mapping recurrent mosaic copy number variation in human neurons," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    5. Zhengyi Zhen & Yu Chen & Haiyan Wang & Huanyin Tang & Haiping Zhang & Haipeng Liu & Ying Jiang & Zhiyong Mao, 2023. "Nuclear cGAS restricts L1 retrotransposition by promoting TRIM41-mediated ORF2p ubiquitination and degradation," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    6. Dustin C. Becht & Brianna J. Klein & Akinori Kanai & Suk Min Jang & Khan L. Cox & Bing-Rui Zhou & Sabrina K. Phanor & Yi Zhang & Ruo-Wen Chen & Christopher C. Ebmeier & Catherine Lachance & Maxime Gal, 2023. "MORF and MOZ acetyltransferases target unmethylated CpG islands through the winged helix domain," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51961-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.