IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v570y2019i7760d10.1038_s41586-019-1248-6.html
   My bibliography  Save this article

Cryo-EM structures of herpes simplex virus type 1 portal vertex and packaged genome

Author

Listed:
  • Yun-Tao Liu

    (University of Science and Technology of China
    University of Science and Technology of China
    University of California, Los Angeles)

  • Jonathan Jih

    (University of California, Los Angeles)

  • Xinghong Dai

    (University of California, Los Angeles
    Immunology and Molecular Genetics, University of California, Los Angeles
    University of California, Los Angeles)

  • Guo-Qiang Bi

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Z. Hong Zhou

    (University of California, Los Angeles
    Immunology and Molecular Genetics, University of California, Los Angeles
    University of California, Los Angeles)

Abstract

Herpesviruses are enveloped viruses that are prevalent in the human population and are responsible for diverse pathologies, including cold sores, birth defects and cancers. They are characterized by a highly pressurized pseudo-icosahedral capsid—with triangulation number (T) equal to 16—encapsidating a tightly packed double-stranded DNA (dsDNA) genome1–3. A key process in the herpesvirus life cycle involves the recruitment of an ATP-driven terminase to a unique portal vertex to recognize, package and cleave concatemeric dsDNA, ultimately giving rise to a pressurized, genome-containing virion4,5. Although this process has been studied in dsDNA phages6–9—with which herpesviruses bear some similarities—a lack of high-resolution in situ structures of genome-packaging machinery has prevented the elucidation of how these multi-step reactions, which require close coordination among multiple actors, occur in an integrated environment. To better define the structural basis of genome packaging and organization in herpes simplex virus type 1 (HSV-1), we developed sequential localized classification and symmetry relaxation methods to process cryo-electron microscopy (cryo-EM) images of HSV-1 virions, which enabled us to decouple and reconstruct hetero-symmetric and asymmetric elements within the pseudo-icosahedral capsid. Here we present in situ structures of the unique portal vertex, genomic termini and ordered dsDNA coils in the capsid spooled around a disordered dsDNA core. We identify tentacle-like helices and a globular complex capping the portal vertex that is not observed in phages, indicative of herpesvirus-specific adaptations in the DNA-packaging process. Finally, our atomic models of portal vertex elements reveal how the fivefold-related capsid accommodates symmetry mismatch imparted by the dodecameric portal—a longstanding mystery in icosahedral viruses—and inform possible DNA-sequence recognition and headful-sensing pathways involved in genome packaging. This work showcases how to resolve symmetry-mismatched elements in a large eukaryotic virus and provides insights into the mechanisms of herpesvirus genome packaging.

Suggested Citation

  • Yun-Tao Liu & Jonathan Jih & Xinghong Dai & Guo-Qiang Bi & Z. Hong Zhou, 2019. "Cryo-EM structures of herpes simplex virus type 1 portal vertex and packaged genome," Nature, Nature, vol. 570(7760), pages 257-261, June.
  • Handle: RePEc:nat:nature:v:570:y:2019:i:7760:d:10.1038_s41586-019-1248-6
    DOI: 10.1038/s41586-019-1248-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-019-1248-6
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-019-1248-6?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Guosong Wang & Zhenghui Zha & Pengfei Huang & Hui Sun & Yang Huang & Maozhou He & Tian Chen & Lina Lin & Zhenqin Chen & Zhibo Kong & Yuqiong Que & Tingting Li & Ying Gu & Hai Yu & Jun Zhang & Qingbing, 2022. "Structures of pseudorabies virus capsids," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Igor Orlov & Stéphane Roche & Sandrine Brasilès & Natalya Lukoyanova & Marie-Christine Vaney & Paulo Tavares & Elena V. Orlova, 2022. "CryoEM structure and assembly mechanism of a bacterial virus genome gatekeeper," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Zhihai Li & Jingjing Pang & Rongchao Gao & Qingxia Wang & Maoyan Zhang & Xuekui Yu, 2023. "Cryo-electron microscopy structures of capsids and in situ portals of DNA-devoid capsids of human cytomegalovirus," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    4. Xudong Jia & Yuanzhu Gao & Yuxuan Huang & Linjun Sun & Siduo Li & Hongmei Li & Xueqing Zhang & Yinyin Li & Jian He & Wenbi Wu & Harikanth Venkannagari & Kai Yang & Matthew L. Baker & Qinfen Zhang, 2023. "Architecture of the baculovirus nucleocapsid revealed by cryo-EM," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Yang Huang & Hui Sun & Shuzhen Wei & Lanlan Cai & Liqin Liu & Yanan Jiang & Jiabao Xin & Zhenqin Chen & Yuqiong Que & Zhibo Kong & Tingting Li & Hai Yu & Jun Zhang & Ying Gu & Qingbing Zheng & Shaowei, 2023. "Structure and proposed DNA delivery mechanism of a marine roseophage," Nature Communications, Nature, vol. 14(1), pages 1-15, 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:nature:v:570:y:2019:i:7760:d:10.1038_s41586-019-1248-6. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.