Protocadherin-1 is essential for cell entry by New World hantaviruses

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, Nicolás A. Muena, Ariel S. Wirchnianski, Elisabeth K. Nyakatura, J. Maximilian Fels, Melinda Ng, Eva Mittler, James Pan, Sushma Bharrhan, Anna Z. Wec, Jonathan R. Lai, Sachdev S. Sidhu, Nicole D. Tischler, Félix A. Rey, Jason Moffat, Thijn R. Brummelkamp (), Zhongde Wang (), John M. Dye () and Kartik Chandran ()
Additional contact information
Rohit K. Jangra: Albert Einstein College of Medicine
Andrew S. Herbert: United States Army Medical Research Institute of Infectious Diseases
Rong Li: Utah State University
Lucas T. Jae: The Netherlands Cancer Institute
Lara M. Kleinfelter: Albert Einstein College of Medicine
Megan M. Slough: Albert Einstein College of Medicine
Sarah L. Barker: University of Toronto
Pablo Guardado-Calvo: Structural Virology Unit and CNRS UMR3569
Gleyder Román-Sosa: Structural Virology Unit and CNRS UMR3569
M. Eugenia Dieterle: Albert Einstein College of Medicine
Ana I. Kuehne: United States Army Medical Research Institute of Infectious Diseases
Nicolás A. Muena: Laboratorio de Virología Molecular
Ariel S. Wirchnianski: United States Army Medical Research Institute of Infectious Diseases
Elisabeth K. Nyakatura: Albert Einstein College of Medicine
J. Maximilian Fels: Albert Einstein College of Medicine
Melinda Ng: Albert Einstein College of Medicine
Eva Mittler: Albert Einstein College of Medicine
James Pan: University of Toronto
Sushma Bharrhan: Albert Einstein College of Medicine
Anna Z. Wec: Albert Einstein College of Medicine
Jonathan R. Lai: Albert Einstein College of Medicine
Sachdev S. Sidhu: University of Toronto
Nicole D. Tischler: Laboratorio de Virología Molecular
Félix A. Rey: Structural Virology Unit and CNRS UMR3569
Jason Moffat: University of Toronto
Thijn R. Brummelkamp: The Netherlands Cancer Institute
Zhongde Wang: Utah State University
John M. Dye: United States Army Medical Research Institute of Infectious Diseases
Kartik Chandran: Albert Einstein College of Medicine

Nature, 2018, vol. 563, issue 7732, 559-563

Abstract: Abstract The zoonotic transmission of hantaviruses from their rodent hosts to humans in North and South America is associated with a severe and frequently fatal respiratory disease, hantavirus pulmonary syndrome (HPS)1,2. No specific antiviral treatments for HPS are available, and no molecular determinants of in vivo susceptibility to hantavirus infection and HPS are known. Here we identify the human asthma-associated gene protocadherin-1 (PCDH1)3–6 as an essential determinant of entry and infection in pulmonary endothelial cells by two hantaviruses that cause HPS, Andes virus (ANDV) and Sin Nombre virus (SNV). In vitro, we show that the surface glycoproteins of ANDV and SNV directly recognize the outermost extracellular repeat domain of PCDH1—a member of the cadherin superfamily7,8—to exploit PCDH1 for entry. In vivo, genetic ablation of PCDH1 renders Syrian golden hamsters highly resistant to a usually lethal ANDV challenge. Targeting PCDH1 could provide strategies to reduce infection and disease caused by New World hantaviruses.

Keywords: Protocadherin (PCDH1); Hantavirus (HTNV); World Hantaviruses; Andes Virus (ANDV); Hantavirus Pulmonary Syndrome (HPS) (search for similar items in EconPapers)
Date: 2018
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Citations: View citations in EconPapers (1)

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DOI: 10.1038/s41586-018-0702-1

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