TY - JOUR
T1 - Protocadherin-1 is essential for cell entry by New World hantaviruses
AU - Jangra, Rohit K.
AU - Herbert, Andrew S.
AU - Li, Rong
AU - Jae, Lucas T.
AU - Kleinfelter, Lara M.
AU - Slough, Megan M.
AU - Barker, Sarah L.
AU - Guardado-Calvo, Pablo
AU - Román-Sosa, Gleyder
AU - Dieterle, M. Eugenia
AU - Kuehne, Ana I.
AU - Muena, Nicolás A.
AU - Wirchnianski, Ariel S.
AU - Nyakatura, Elisabeth K.
AU - Fels, J. Maximilian
AU - Ng, Melinda
AU - Mittler, Eva
AU - Pan, James
AU - Bharrhan, Sushma
AU - Wec, Anna Z.
AU - Lai, Jonathan R.
AU - Sidhu, Sachdev S.
AU - Tischler, Nicole D.
AU - Rey, Félix A.
AU - Moffat, Jason
AU - Brummelkamp, Thijn R.
AU - Wang, Zhongde
AU - Dye, John M.
AU - Chandran, Kartik
N1 - Publisher Copyright:
© 2018, Springer Nature Limited.
PY - 2018/11/22
Y1 - 2018/11/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85056950594&partnerID=8YFLogxK
U2 - 10.1038/s41586-018-0702-1
DO - 10.1038/s41586-018-0702-1
M3 - Article
C2 - 30464266
AN - SCOPUS:85056950594
SN - 0028-0836
VL - 563
SP - 559
EP - 563
JO - Nature
JF - Nature
IS - 7732
ER -