Dog nectin-4 is an epithelial cell receptor for canine distemper virus that facilitates virus entry and syncytia formation

Ryan S. Noyce; Sebastien Delpeut; Christopher D. Richardson

doi:10.1016/j.virol.2012.11.011

Dog nectin-4 is an epithelial cell receptor for canine distemper virus that facilitates virus entry and syncytia formation

Ryan S. Noyce, Sebastien Delpeut, Christopher D. Richardson

Medicine

Research output: Contribution to journal › Article › peer-review

81 Citations (Scopus)

Abstract

Canine distemper virus (CDV) was shown to use dog nectin-4 as a receptor to gain entry into epithelial cells. RNA from dog placenta or MDCK kidney cells was isolated and cDNAs were prepared. Two splice variants of dog nectin-4 were identified. A deletion of 25 amino acids was found in the cytoplasmic domain of dog nectin-4 from MDCK cells, corresponding to a splice variant that is also seen in murine nectin-4, and did not affect its role as a receptor. Both dog nectin-4 and human nectin-4 could function as an entry factor for CDV containing an EGFP reporter gene. Inhibition of dog nectin-4 expression by RNAi or nectin-4 antibodies decreased CDV titers and EGFP fluorescence. Finally, dog nectin-4 also promotes syncytia formation, which could be inhibited by siRNA treatment. These data confirm that dog nectin-4 can be used by CDV to gain entry into epithelial cells, and facilitate virus spread.

Original language	English
Pages (from-to)	210-220
Number of pages	11
Journal	Virology
Volume	436
Issue number	1
DOIs	https://doi.org/10.1016/j.virol.2012.11.011
Publication status	Published - Feb 5 2013

Bibliographical note

Funding Information:
We would like to thank Roberto Cattaneo and Veronika von Messling for giving us IC323-eGFP wtMeV and wtCDV 5804PeH, respectively. David Hoskin and Craig McCormick generously supplied us with MCF7, MDA-MB231, and MDCK cells that were used in these studies. We thank Gary Sisson for expert technical assistance. Placenta from a Labrador retriever was obtained from Don Bates of Doindogs Kennel, Dartmouth, Nova Scotia and placenta from a papillon was acquired with the help of Stephanie Callahan-Corkum and Mary Taplin of Country Critter Sitters, Seaforth, Nova Scotia. This work was supported by grants from the Canadian Institutes for Health Research ( CIHR MOP 10638 ; CIHR MOP 114949 ) and Nova Scotia Health Research Foundation (Grant #1200 ). C.D.R. is a Canada Research Chair (Tier I) in Vaccinology and Viral Therapeutics and received an equipment grant from the Canadian Foundation for Innovation. R.S.N. is supported by a CIHR Banting Postdoctoral Fellowship and held a trainee award from the Beatrice Hunter Cancer Research Institute with funds provided by the Canadian Breast Cancer Foundation—Atlantic Region as part of The Terry Fox Strategic Health Research Training Program in Cancer Research in CIHR.

ASJC Scopus Subject Areas

Virology

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10.1016/j.virol.2012.11.011

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title = "Dog nectin-4 is an epithelial cell receptor for canine distemper virus that facilitates virus entry and syncytia formation",

abstract = "Canine distemper virus (CDV) was shown to use dog nectin-4 as a receptor to gain entry into epithelial cells. RNA from dog placenta or MDCK kidney cells was isolated and cDNAs were prepared. Two splice variants of dog nectin-4 were identified. A deletion of 25 amino acids was found in the cytoplasmic domain of dog nectin-4 from MDCK cells, corresponding to a splice variant that is also seen in murine nectin-4, and did not affect its role as a receptor. Both dog nectin-4 and human nectin-4 could function as an entry factor for CDV containing an EGFP reporter gene. Inhibition of dog nectin-4 expression by RNAi or nectin-4 antibodies decreased CDV titers and EGFP fluorescence. Finally, dog nectin-4 also promotes syncytia formation, which could be inhibited by siRNA treatment. These data confirm that dog nectin-4 can be used by CDV to gain entry into epithelial cells, and facilitate virus spread.",

author = "Noyce, {Ryan S.} and Sebastien Delpeut and Richardson, {Christopher D.}",

note = "Funding Information: We would like to thank Roberto Cattaneo and Veronika von Messling for giving us IC323-eGFP wtMeV and wtCDV 5804PeH, respectively. David Hoskin and Craig McCormick generously supplied us with MCF7, MDA-MB231, and MDCK cells that were used in these studies. We thank Gary Sisson for expert technical assistance. Placenta from a Labrador retriever was obtained from Don Bates of Doindogs Kennel, Dartmouth, Nova Scotia and placenta from a papillon was acquired with the help of Stephanie Callahan-Corkum and Mary Taplin of Country Critter Sitters, Seaforth, Nova Scotia. This work was supported by grants from the Canadian Institutes for Health Research ( CIHR MOP 10638 ; CIHR MOP 114949 ) and Nova Scotia Health Research Foundation (Grant #1200 ). C.D.R. is a Canada Research Chair (Tier I) in Vaccinology and Viral Therapeutics and received an equipment grant from the Canadian Foundation for Innovation. R.S.N. is supported by a CIHR Banting Postdoctoral Fellowship and held a trainee award from the Beatrice Hunter Cancer Research Institute with funds provided by the Canadian Breast Cancer Foundation—Atlantic Region as part of The Terry Fox Strategic Health Research Training Program in Cancer Research in CIHR.",

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N2 - Canine distemper virus (CDV) was shown to use dog nectin-4 as a receptor to gain entry into epithelial cells. RNA from dog placenta or MDCK kidney cells was isolated and cDNAs were prepared. Two splice variants of dog nectin-4 were identified. A deletion of 25 amino acids was found in the cytoplasmic domain of dog nectin-4 from MDCK cells, corresponding to a splice variant that is also seen in murine nectin-4, and did not affect its role as a receptor. Both dog nectin-4 and human nectin-4 could function as an entry factor for CDV containing an EGFP reporter gene. Inhibition of dog nectin-4 expression by RNAi or nectin-4 antibodies decreased CDV titers and EGFP fluorescence. Finally, dog nectin-4 also promotes syncytia formation, which could be inhibited by siRNA treatment. These data confirm that dog nectin-4 can be used by CDV to gain entry into epithelial cells, and facilitate virus spread.

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Dog nectin-4 is an epithelial cell receptor for canine distemper virus that facilitates virus entry and syncytia formation

Abstract

Bibliographical note

ASJC Scopus Subject Areas

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