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Single-nucleotide polymorphisms in human NPC1 influence filovirus entry into cells

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Title: Single-nucleotide polymorphisms in human NPC1 influence filovirus entry into cells
Authors: Kondoh, Tatsunari Browse this author
Letko, Michael Browse this author
Munster, Vincent J. Browse this author
Manzoor, Rashid Browse this author
Maruyama, Junki Browse this author
Furuyama, Wakako Browse this author
Miyamoto, Hiroko Browse this author
Shigeno, Asako Browse this author
Fujikura, Daisuke Browse this author →KAKEN DB
Takadate, Yoshihiro Browse this author
Yoshida, Reiko Browse this author →KAKEN DB
Igarashi, Manabu Browse this author →KAKEN DB
Feldmann, Heinz Browse this author
Marzi, Andrea Browse this author
Takada, Ayato Browse this author →KAKEN DB
Keywords: Ebolavirus
Niemann-Pick C1 (NPC1)
Single-nucleotide polymorphism (SNP)
NPC1-knockout Vero E6 (Vero E6/NPC1-KO)
Issue Date: 15-Dec-2018
Publisher: Oxford University Press
Journal Title: Journal of Infectious Diseases
Volume: 218
Issue: suppl 5
Start Page: S397
End Page: S402
Publisher DOI: 10.1093/infdis/jiy248
PMID: 30010949
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.
Rights: This is a pre-copyedited, author-produced version of an article accepted for publication in The Journal of Infectious Diseases following peer review. The version of record Volume 218 Issue suppl_5, S397–S402, 2018 is available online at:
Type: article (author version)
Appears in Collections:人獣共通感染症リサーチセンター (Research Center for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
国際連携研究教育局 : GI-CoRE (Global Institution for Collaborative Research and Education : GI-CoRE) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 高田 礼人

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