IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-35898-2.html
   My bibliography  Save this article

Barrier-to-autointegration factor 1 promotes gammaherpesvirus reactivation from latency

Author

Listed:
  • Grant Broussard

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Guoxin Ni

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Zhigang Zhang

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Qian Li

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Patricio Cano

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Dirk P. Dittmer

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Blossom Damania

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

Abstract

Gammaherpesviruses, including Kaposi sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), are DNA viruses that are globally associated with human cancers and establish lifelong latency in the human population. Detection of gammaherpesviral infection by the cGAS-STING innate immune DNA-sensing pathway is critical for suppressing viral reactivation from latency, a process that promotes viral pathogenesis and transmission. We report that barrier-to-autointegration factor 1 (BAF)-mediated suppression of the cGAS-STING signaling pathway is necessary for reactivation of KSHV and EBV. We demonstrate a role for BAF in destabilizing cGAS expression and show that inhibiting BAF expression in latently infected, reactivating, or uninfected cells leads to increased type I interferon-mediated antiviral responses and decreased viral replication. Furthermore, BAF overexpression resulted in decreased cGAS expression at the protein level. These results establish BAF as a key regulator of the lifecycle of gammaherpesviruses and a potential target for treating viral infections and malignancies.

Suggested Citation

  • Grant Broussard & Guoxin Ni & Zhigang Zhang & Qian Li & Patricio Cano & Dirk P. Dittmer & Blossom Damania, 2023. "Barrier-to-autointegration factor 1 promotes gammaherpesvirus reactivation from latency," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35898-2
    DOI: 10.1038/s41467-023-35898-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-35898-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-35898-2?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. Tobias V. Lanz & R. Camille Brewer & Peggy P. Ho & Jae-Seung Moon & Kevin M. Jude & Daniel Fernandez & Ricardo A. Fernandes & Alejandro M. Gomez & Gabriel-Stefan Nadj & Christopher M. Bartley & Ryan D, 2022. "Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM," Nature, Nature, vol. 603(7900), pages 321-327, March.
    2. Junji Xing & Ao Zhang & Hua Zhang & Jin Wang & Xian Chang Li & Mu-Sheng Zeng & Zhiqiang Zhang, 2017. "TRIM29 promotes DNA virus infections by inhibiting innate immune response," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    3. A. Phillip West & William Khoury-Hanold & Matthew Staron & Michal C. Tal & Cristiana M. Pineda & Sabine M. Lang & Megan Bestwick & Brett A. Duguay & Nuno Raimundo & Donna A. MacDuff & Susan M. Kaech &, 2015. "Mitochondrial DNA stress primes the antiviral innate immune response," Nature, Nature, vol. 520(7548), pages 553-557, April.
    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. Zhibin Lin & Peijun Yang & Yufeng Hu & Hao Xu & Juanli Duan & Fei He & Kefeng Dou & Lin Wang, 2023. "RING finger protein 13 protects against nonalcoholic steatohepatitis by targeting STING-relayed signaling pathways," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Daipayan Banerjee & Kurt Langberg & Salar Abbas & Eric Odermatt & Praveen Yerramothu & Martin Volaric & Matthew A. Reidenbach & Kathy J. Krentz & C. Dustin Rubinstein & David L. Brautigan & Tarek Abba, 2021. "A non-canonical, interferon-independent signaling activity of cGAMP triggers DNA damage response signaling," Nature Communications, Nature, vol. 12(1), pages 1-24, December.
    3. Zoë P. Van Acker & Anika Perdok & Ruben Hellemans & Katherine North & Inge Vorsters & Cedric Cappel & Jonas Dehairs & Johannes V. Swinnen & Ragna Sannerud & Marine Bretou & Markus Damme & Wim Annaert, 2023. "Phospholipase D3 degrades mitochondrial DNA to regulate nucleotide signaling and APP metabolism," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    4. Maximilian Hirschenberger & Alice Lepelley & Ulrich Rupp & Susanne Klute & Victoria Hunszinger & Lennart Koepke & Veronika Merold & Blaise Didry-Barca & Fanny Wondany & Tim Bergner & Tatiana Moreau & , 2023. "ARF1 prevents aberrant type I interferon induction by regulating STING activation and recycling," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    5. Vaibhav Sidarala & Jie Zhu & Elena Levi-D’Ancona & Gemma L. Pearson & Emma C. Reck & Emily M. Walker & Brett A. Kaufman & Scott A. Soleimanpour, 2022. "Mitofusin 1 and 2 regulation of mitochondrial DNA content is a critical determinant of glucose homeostasis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    6. Kate M. MacDonald & Shirony Nicholson-Puthenveedu & Maha M. Tageldein & Sarika Khasnis & Cheryl H. Arrowsmith & Shane M. Harding, 2023. "Antecedent chromatin organization determines cGAS recruitment to ruptured micronuclei," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    7. Sarah Rösing & Fabian Ullrich & Susann Meisterfeld & Franziska Schmidt & Laura Mlitzko & Marijana Croon & Ryan G Nattrass & Nadia Eberl & Julia Mahlberg & Martin Schlee & Anja Wieland & Philipp Simon , 2024. "Chronic endoplasmic reticulum stress in myotonic dystrophy type 2 promotes autoimmunity via mitochondrial DNA release," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    8. Junying Wang & Wenting Lu & Jerry Zhang & Yong Du & Mingli Fang & Ao Zhang & Gabriel Sungcad & Samantha Chon & Junji Xing, 2024. "Loss of TRIM29 mitigates viral myocarditis by attenuating PERK-driven ER stress response in male mice," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    9. Andrea Irazoki & Isabel Gordaliza-Alaguero & Emma Frank & Nikolaos Nikiforos Giakoumakis & Jordi Seco & Manuel Palacín & Anna Gumà & Lykke Sylow & David Sebastián & Antonio Zorzano, 2023. "Disruption of mitochondrial dynamics triggers muscle inflammation through interorganellar contacts and mitochondrial DNA mislocation," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    10. Naijun Miao & Zhuning Wang & Qinlan Wang & Hongyan Xie & Ninghao Yang & Yanzhe Wang & Jin Wang & Haixia Kang & Wenjuan Bai & Yuanyuan Wang & Rui He & Kepeng Yan & Yang Wang & Qiongyi Hu & Zhaoyuan Liu, 2023. "Oxidized mitochondrial DNA induces gasdermin D oligomerization in systemic lupus erythematosus," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    11. Nathan Meade & Helen K. Toreev & Ram P. Chakrabarty & Charles R. Hesser & Chorong Park & Navdeep S. Chandel & Derek Walsh, 2023. "The poxvirus F17 protein counteracts mitochondrially orchestrated antiviral responses," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    12. Xintao Tu & Ting-Ting Chu & Devon Jeltema & Kennady Abbott & Kun Yang & Cong Xing & Jie Han & Nicole Dobbs & Nan Yan, 2022. "Interruption of post-Golgi STING trafficking activates tonic interferon signaling," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    13. Ying Huang & Geng Qin & TingTing Cui & Chuanqi Zhao & Jinsong Ren & Xiaogang Qu, 2023. "A bimetallic nanoplatform for STING activation and CRISPR/Cas mediated depletion of the methionine transporter in cancer cells restores anti-tumor immune responses," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    14. Xiaoquan Wang & Youqiao Wang & Anqi Cao & Qinhong Luo & Daoyuan Chen & Weiqi Zhao & Jun Xu & Qinkai Li & Xianzhang Bu & Junmin Quan, 2023. "Development of cyclopeptide inhibitors of cGAS targeting protein-DNA interaction and phase separation," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    15. Vijayendra Dasari & Lisa K. McNeil & Kirrilee Beckett & Matthew Solomon & George Ambalathingal & T. Le Thuy & Archana Panikkar & Caitlyn Smith & Martin P. Steinbuck & Aniela Jakubowski & Lochana M. Se, 2023. "Lymph node targeted multi-epitope subunit vaccine promotes effective immunity to EBV in HLA-expressing mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    16. Hayden Weng Siong Tan & Guang Lu & Han Dong & Yik-Lam Cho & Auginia Natalia & Liming Wang & Charlene Chan & Dennis Kappei & Reshma Taneja & Shuo-Chien Ling & Huilin Shao & Shih-Yin Tsai & Wen-Xing Din, 2022. "A degradative to secretory autophagy switch mediates mitochondria clearance in the absence of the mATG8-conjugation machinery," Nature Communications, Nature, vol. 13(1), pages 1-17, 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:14:y:2023:i:1:d:10.1038_s41467-023-35898-2. 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.