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 journalArticle

12 Citations (Scopus)

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 1 2018

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Hantavirus
Hantavirus Pulmonary Syndrome
Sin Nombre virus
Hantavirus Infections
South America
Mesocricetus
Membrane Glycoproteins
Zoonoses
Cadherins
North America
Infection
Antiviral Agents
Rodentia
Asthma
Endothelial Cells
Lung
Genes

ASJC Scopus subject areas

  • General

Cite this

Jangra, R. K., Herbert, A. S., Li, R., Jae, L. T., Kleinfelter, L. M., Slough, M. M., ... 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

Protocadherin-1 is essential for cell entry by New World hantaviruses. / Jangra, Rohit K.; Herbert, Andrew S.; Li, Rong; Jae, Lucas T.; Kleinfelter, Lara M.; Slough, Megan M.; Barker, Sarah L.; Guardado-Calvo, Pablo; Román-Sosa, Gleyder; Dieterle, M. Eugenia; Kuehne, Ana I.; Muena, Nicolás A.; Wirchnianski, Ariel S.; Nyakatura, Elisabeth K.; Fels, J. Maximilian; Ng, Melinda; Mittler, Eva; Pan, James; Bharrhan, Sushma; Wec, Anna Z.; Lai, Jonathan R.; Sidhu, Sachdev S.; Tischler, Nicole D.; Rey, Félix A.; Moffat, Jason; Brummelkamp, Thijn R.; Wang, Zhongde; Dye, John M.; Chandran, Kartik.

In: Nature, Vol. 563, No. 7732, 01.11.2018, p. 559-563.

Research output: Contribution to journalArticle

Jangra, RK, Herbert, AS, Li, R, Jae, LT, Kleinfelter, LM, Slough, MM, Barker, SL, Guardado-Calvo, P, Román-Sosa, G, Dieterle, ME, Kuehne, AI, Muena, NA, Wirchnianski, AS, Nyakatura, EK, Fels, JM, Ng, M, Mittler, E, Pan, J, Bharrhan, S, Wec, AZ, Lai, JR, Sidhu, SS, Tischler, ND, Rey, FA, Moffat, J, Brummelkamp, TR, Wang, Z, Dye, JM & Chandran, K 2018, 'Protocadherin-1 is essential for cell entry by New World hantaviruses', Nature, vol. 563, no. 7732, pp. 559-563. https://doi.org/10.1038/s41586-018-0702-1
Jangra RK, Herbert AS, Li R, Jae LT, Kleinfelter LM, Slough MM et al. Protocadherin-1 is essential for cell entry by New World hantaviruses. Nature. 2018 Nov 1;563(7732):559-563. https://doi.org/10.1038/s41586-018-0702-1
Jangra, Rohit K. ; Herbert, Andrew S. ; Li, Rong ; Jae, Lucas T. ; Kleinfelter, Lara M. ; Slough, Megan M. ; Barker, Sarah L. ; Guardado-Calvo, Pablo ; Román-Sosa, Gleyder ; Dieterle, M. Eugenia ; Kuehne, Ana I. ; Muena, Nicolás A. ; Wirchnianski, Ariel S. ; Nyakatura, Elisabeth K. ; Fels, J. Maximilian ; Ng, Melinda ; Mittler, Eva ; Pan, James ; Bharrhan, Sushma ; Wec, Anna Z. ; Lai, Jonathan R. ; Sidhu, Sachdev S. ; Tischler, Nicole D. ; Rey, Félix A. ; Moffat, Jason ; Brummelkamp, Thijn R. ; Wang, Zhongde ; Dye, John M. ; Chandran, Kartik. / Protocadherin-1 is essential for cell entry by New World hantaviruses. In: Nature. 2018 ; Vol. 563, No. 7732. pp. 559-563.
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AU - Slough, Megan M.

AU - Barker, Sarah L.

AU - Guardado-Calvo, Pablo

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AU - Moffat, Jason

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