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Nature. 2018 Nov;563(7732):559-563. doi: 10.1038/s41586-018-0702-1. Epub 2018 Nov 21.

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

Author information

1
Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.
2
United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.
3
Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT, USA.
4
Oncode Institute, Division of Biochemistry, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
5
Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
6
Donnelly Centre and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
7
Institut Pasteur, Structural Virology Unit and CNRS UMR3569, Paris, France.
8
Fundación Ciencia & Vida, Laboratorio de Virología Molecular, Santiago, Chile.
9
Department of Microbiology and Immunology and Department of Biochemistry, Albert Einstein College of Medicine, New York, NY, USA.
10
Department of Biochemistry, Albert Einstein College of Medicine, New York, NY, USA.
11
Adimab LLC, Lebanon, NH, USA.
12
Canadian Institute for Advanced Research, Toronto, Ontario, Canada.
13
Oncode Institute, Division of Biochemistry, The Netherlands Cancer Institute, Amsterdam, The Netherlands. t.brummelkamp@nki.nl.
14
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. t.brummelkamp@nki.nl.
15
Cancer GenomiCs.nl (CGC.nl), Amsterdam, The Netherlands. t.brummelkamp@nki.nl.
16
Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT, USA. zonda.wang@usu.edu.
17
United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA. john.m.dye1.civ@mail.mil.
18
Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA. kartik.chandran@einstein.yu.edu.

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.

PMID:
30464266
PMCID:
PMC6556216
DOI:
10.1038/s41586-018-0702-1
[Indexed for MEDLINE]
Free PMC Article

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