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Two point mutations in protocadherin-1 disrupt hantavirus recognition and afford protection against lethal infection

Author

Listed:
  • Megan M. Slough

    (Albert Einstein College of Medicine)

  • Rong Li

    (Utah State University)

  • Andrew S. Herbert

    (United States Army Medical Research Institute of Infectious Diseases)

  • Gorka Lasso

    (Albert Einstein College of Medicine)

  • Ana I. Kuehne

    (United States Army Medical Research Institute of Infectious Diseases)

  • Stephanie R. Monticelli

    (United States Army Medical Research Institute of Infectious Diseases
    The Geneva Foundation)

  • Russell R. Bakken

    (United States Army Medical Research Institute of Infectious Diseases)

  • Yanan Liu

    (Utah State University)

  • Agnidipta Ghosh

    (Albert Einstein College of Medicine)

  • Alicia M. Moreau

    (United States Army Medical Research Institute of Infectious Diseases)

  • Xiankun Zeng

    (United States Army Medical Research Institute of Infectious Diseases)

  • Félix A. Rey

    (Université Paris Cité, CNRS UMR3569, Structural Virology Unit)

  • Pablo Guardado-Calvo

    (Université Paris Cité, CNRS UMR3569, Structural Virology Unit
    Université Paris Cité, Structural Biology of Infectious Diseases Unit)

  • Steven C. Almo

    (Albert Einstein College of Medicine)

  • John M. Dye

    (United States Army Medical Research Institute of Infectious Diseases)

  • Rohit K. Jangra

    (Albert Einstein College of Medicine
    Louisiana State University Health Sciences Center-Shreveport)

  • Zhongde Wang

    (Utah State University)

  • Kartik Chandran

    (Albert Einstein College of Medicine)

Abstract

Andes virus (ANDV) and Sin Nombre virus (SNV) are the etiologic agents of severe hantavirus cardiopulmonary syndrome (HCPS) in the Americas for which no FDA-approved countermeasures are available. Protocadherin-1 (PCDH1), a cadherin-superfamily protein recently identified as a critical host factor for ANDV and SNV, represents a new antiviral target; however, its precise role remains to be elucidated. Here, we use computational and experimental approaches to delineate the binding surface of the hantavirus glycoprotein complex on PCDH1’s first extracellular cadherin repeat domain. Strikingly, a single amino acid residue in this PCDH1 surface influences the host species-specificity of SNV glycoprotein-PCDH1 interaction and cell entry. Mutation of this and a neighboring residue substantially protects Syrian hamsters from pulmonary disease and death caused by ANDV. We conclude that PCDH1 is a bona fide entry receptor for ANDV and SNV whose direct interaction with hantavirus glycoproteins could be targeted to develop new interventions against HCPS.

Suggested Citation

  • Megan M. Slough & Rong Li & Andrew S. Herbert & Gorka Lasso & Ana I. Kuehne & Stephanie R. Monticelli & Russell R. Bakken & Yanan Liu & Agnidipta Ghosh & Alicia M. Moreau & Xiankun Zeng & Félix A. Rey, 2023. "Two point mutations in protocadherin-1 disrupt hantavirus recognition and afford protection against lethal infection," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40126-y
    DOI: 10.1038/s41467-023-40126-y
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    References listed on IDEAS

    as
    1. Rohit K. Jangra & Andrew S. Herbert & Rong Li & Lucas T. Jae & Lara M. Kleinfelter & Megan M. Slough & Sarah L. Barker & Pablo Guardado-Calvo & Gleyder Román-Sosa & M. Eugenia Dieterle & Ana I. Kuehne, 2018. "Protocadherin-1 is essential for cell entry by New World hantaviruses," Nature, Nature, vol. 563(7732), pages 559-563, November.
    2. Shinya Yamada & Yasuo Suzuki & Takashi Suzuki & Mai Q. Le & Chairul A. Nidom & Yuko Sakai-Tagawa & Yukiko Muramoto & Mutsumi Ito & Maki Kiso & Taisuke Horimoto & Kyoko Shinya & Toshihiko Sawada & Mako, 2006. "Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors," Nature, Nature, vol. 444(7117), pages 378-382, November.
    3. Wenhui Li & Michael J. Moore & Natalya Vasilieva & Jianhua Sui & Swee Kee Wong & Michael A. Berne & Mohan Somasundaran & John L. Sullivan & Katherine Luzuriaga & Thomas C. Greenough & Hyeryun Choe & M, 2003. "Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus," Nature, Nature, vol. 426(6965), pages 450-454, November.
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