Single-Nucleotide Polymorphisms in Human NPC1 Influence Filovirus Entry into Cells

Tatsunari Kondoh; Michael Letko; Vincent J. Munster; Rashid Manzoor; Junki Maruyama; Wakako Furuyama; Hiroko Miyamoto; Asako Shigeno; Daisuke Fujikura; Yoshihiro Takadate; Reiko Yoshida; Manabu Igarashi; Heinz Feldmann; Andrea Marzi; Ayato Takada

doi:10.1093/infdis/jiy248

Single-Nucleotide Polymorphisms in Human NPC1 Influence Filovirus Entry into Cells

Tatsunari Kondoh, Michael Letko, Vincent J. Munster, Rashid Manzoor, Junki Maruyama, Wakako Furuyama, Hiroko Miyamoto, Asako Shigeno, Daisuke Fujikura, Yoshihiro Takadate, Reiko Yoshida, Manabu Igarashi, Heinz Feldmann, Andrea Marzi, Ayato Takada

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

9 Scopus citations

Abstract

Niemann-Pick C1 (NPC1), a host receptor involved in the envelope glycoprotein (GP)-mediated entry of filoviruses into cells, is believed to be a major determinant of cell susceptibility to filovirus infection. It is known that proteolytically digested Ebola virus (EBOV) GP interacts with 2 protruding loops in domain C of NPC1. Using previously published structural data and the National Center for Biotechnology Information Single-Nucleotide Polymorphism (SNP) database, we identified 10 naturally occurring missense SNPs in human NPC1. To investigate whether these SNPs affect cell susceptibility to filovirus infection, we generated Vero E6 cell lines stably expressing NPC1 with SNP substitutions and compared their susceptibility to vesicular stomatitis virus pseudotyped with filovirus GPs and infectious EBOV. We found that some of the substitutions resulted in reduced susceptibility to filoviruses, as indicated by the lower titers and smaller plaque/focus sizes of the viruses. Our data suggest that human NPC1 SNPs may likely affect host susceptibility to filoviruses.

Original language	English (US)
Pages (from-to)	S397-S402
Journal	Journal of Infectious Diseases
Volume	218
DOIs	https://doi.org/10.1093/infdis/jiy248
State	Published - Nov 22 2018
Externally published	Yes

Keywords

Ebolavirus
Marburgvirus
NPC1-knockout Vero E6 (Vero E6/NPC1-KO).
Niemann-Pick C1 (NPC1)
single-nucleotide polymorphism (SNP)

ASJC Scopus subject areas

Immunology and Allergy
Infectious Diseases

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10.1093/infdis/jiy248

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Kondoh, T., Letko, M., Munster, V. J., Manzoor, R., Maruyama, J., Furuyama, W., Miyamoto, H., Shigeno, A., Fujikura, D., Takadate, Y., Yoshida, R., Igarashi, M., Feldmann, H., Marzi, A., & Takada, A. (2018). Single-Nucleotide Polymorphisms in Human NPC1 Influence Filovirus Entry into Cells. Journal of Infectious Diseases, 218, S397-S402. https://doi.org/10.1093/infdis/jiy248

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title = "Single-Nucleotide Polymorphisms in Human NPC1 Influence Filovirus Entry into Cells",

abstract = "Niemann-Pick C1 (NPC1), a host receptor involved in the envelope glycoprotein (GP)-mediated entry of filoviruses into cells, is believed to be a major determinant of cell susceptibility to filovirus infection. It is known that proteolytically digested Ebola virus (EBOV) GP interacts with 2 protruding loops in domain C of NPC1. Using previously published structural data and the National Center for Biotechnology Information Single-Nucleotide Polymorphism (SNP) database, we identified 10 naturally occurring missense SNPs in human NPC1. To investigate whether these SNPs affect cell susceptibility to filovirus infection, we generated Vero E6 cell lines stably expressing NPC1 with SNP substitutions and compared their susceptibility to vesicular stomatitis virus pseudotyped with filovirus GPs and infectious EBOV. We found that some of the substitutions resulted in reduced susceptibility to filoviruses, as indicated by the lower titers and smaller plaque/focus sizes of the viruses. Our data suggest that human NPC1 SNPs may likely affect host susceptibility to filoviruses.",

keywords = "Ebolavirus, Marburgvirus, NPC1-knockout Vero E6 (Vero E6/NPC1-KO)., Niemann-Pick C1 (NPC1), single-nucleotide polymorphism (SNP)",

author = "Tatsunari Kondoh and Michael Letko and Munster, {Vincent J.} and Rashid Manzoor and Junki Maruyama and Wakako Furuyama and Hiroko Miyamoto and Asako Shigeno and Daisuke Fujikura and Yoshihiro Takadate and Reiko Yoshida and Manabu Igarashi and Heinz Feldmann and Andrea Marzi and Ayato Takada",

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doi = "10.1093/infdis/jiy248",

language = "English (US)",

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AU - Kondoh, Tatsunari

AU - Letko, Michael

AU - Munster, Vincent J.

AU - Manzoor, Rashid

AU - Maruyama, Junki

AU - Furuyama, Wakako

AU - Miyamoto, Hiroko

AU - Shigeno, Asako

AU - Fujikura, Daisuke

AU - Takadate, Yoshihiro

AU - Yoshida, Reiko

AU - Igarashi, Manabu

AU - Feldmann, Heinz

AU - Marzi, Andrea

AU - Takada, Ayato

PY - 2018/11/22

Y1 - 2018/11/22

N2 - Niemann-Pick C1 (NPC1), a host receptor involved in the envelope glycoprotein (GP)-mediated entry of filoviruses into cells, is believed to be a major determinant of cell susceptibility to filovirus infection. It is known that proteolytically digested Ebola virus (EBOV) GP interacts with 2 protruding loops in domain C of NPC1. Using previously published structural data and the National Center for Biotechnology Information Single-Nucleotide Polymorphism (SNP) database, we identified 10 naturally occurring missense SNPs in human NPC1. To investigate whether these SNPs affect cell susceptibility to filovirus infection, we generated Vero E6 cell lines stably expressing NPC1 with SNP substitutions and compared their susceptibility to vesicular stomatitis virus pseudotyped with filovirus GPs and infectious EBOV. We found that some of the substitutions resulted in reduced susceptibility to filoviruses, as indicated by the lower titers and smaller plaque/focus sizes of the viruses. Our data suggest that human NPC1 SNPs may likely affect host susceptibility to filoviruses.

AB - Niemann-Pick C1 (NPC1), a host receptor involved in the envelope glycoprotein (GP)-mediated entry of filoviruses into cells, is believed to be a major determinant of cell susceptibility to filovirus infection. It is known that proteolytically digested Ebola virus (EBOV) GP interacts with 2 protruding loops in domain C of NPC1. Using previously published structural data and the National Center for Biotechnology Information Single-Nucleotide Polymorphism (SNP) database, we identified 10 naturally occurring missense SNPs in human NPC1. To investigate whether these SNPs affect cell susceptibility to filovirus infection, we generated Vero E6 cell lines stably expressing NPC1 with SNP substitutions and compared their susceptibility to vesicular stomatitis virus pseudotyped with filovirus GPs and infectious EBOV. We found that some of the substitutions resulted in reduced susceptibility to filoviruses, as indicated by the lower titers and smaller plaque/focus sizes of the viruses. Our data suggest that human NPC1 SNPs may likely affect host susceptibility to filoviruses.

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KW - Marburgvirus

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KW - single-nucleotide polymorphism (SNP)

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Single-Nucleotide Polymorphisms in Human NPC1 Influence Filovirus Entry into Cells

Abstract

Keywords

ASJC Scopus subject areas

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