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. WecJonathan R. Lai, Sachdev S. Sidhu, Nicole D. Tischler, Félix A. Rey, Jason Moffat, Thijn R. Brummelkamp, Zhongde Wang, John M. Dye, Kartik Chandran

Research output: Contribution to journalLetter

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)559-563
Number of pages5
JournalNature
Volume563
Issue number7732
DOIs
StatePublished - Nov 22 2018

ASJC Scopus subject areas

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    Jangra, R. K., Herbert, A. S., Li, R., Jae, L. T., Kleinfelter, L. M., Slough, M. M., Barker, S. L., Guardado-Calvo, P., Román-Sosa, G., Dieterle, M. E., Kuehne, A. I., Muena, N. A., Wirchnianski, A. S., Nyakatura, E. K., Fels, J. M., Ng, M., Mittler, E., Pan, J., Bharrhan, S., ... Chandran, K. (2018). Protocadherin-1 is essential for cell entry by New World hantaviruses. Nature, 563(7732), 559-563. https://doi.org/10.1038/s41586-018-0702-1