@article{8b1698bbc942421ba6ed34f25b9fb706,
title = "Niemann-Pick C1 Heterogeneity of Bat Cells Controls Filovirus Tropism",
abstract = "Fruit bats are suspected to be natural hosts of filoviruses, including Ebola virus (EBOV) and Marburg virus (MARV). Interestingly, however, previous studies suggest that these viruses have different tropisms depending on the bat species. Here, we show a molecular basis underlying the host-range restriction of filoviruses. We find that bat-derived cell lines FBKT1 and ZFBK13-76E show preferential susceptibility to EBOV and MARV, respectively, whereas the other bat cell lines tested are similarly infected with both viruses. In FBKT1 and ZFBK13-76E, unique amino acid (aa) sequences are found in the Niemann-Pick C1 (NPC1) protein, one of the cellular receptors interacting with the filovirus glycoprotein (GP). These aa residues, as well as a few aa differences between EBOV and MARV GPs, are crucial for the differential susceptibility to filoviruses. Taken together, our findings indicate that the heterogeneity of bat NPC1 orthologs is an important factor controlling filovirus species-specific host tropism. Differential susceptibilities of bats to filoviruses have been suggested. Takadate et al. compare structures of the filovirus receptor among a variety of bat cell lines and discover a molecular mechanism determining their susceptibility to Ebola and Marburg viruses, providing information for understanding the ecology of filoviruses.",
keywords = "Ebola virus, Marburg virus, Niemann-Pick C1, bat, filovirus, glycoprotein, host range, natural host, receptor, virus-host interaction",
author = "Yoshihiro Takadate and Tatsunari Kondoh and Manabu Igarashi and Junki Maruyama and Rashid Manzoor and Hirohito Ogawa and Masahiro Kajihara and Wakako Furuyama and Masahiro Sato and Hiroko Miyamoto and Reiko Yoshida and Hill, {Terence E.} and Freiberg, {Alexander N.} and Heinz Feldmann and Andrea Marzi and Ayato Takada",
note = "Funding Information: Infectious work with wild-type EBOV and MARV was performed in the Galveston National Laboratory biosafety level 4 (BSL-4) laboratory at the University of Texas Medical Branch and in the BSL-4 laboratory at the Integrated Research Facility of the Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH; Hamilton, MT). Experiments were performed following the standard operating procedures approved by the Institutional Biosafety Committees. Funding Information: We thank Ms. A. Shigeno for technical assistance, Drs. K. Maeda and E. Hondo for providing bat-derived cell lines, and Mr. K. Barrymore for editing the manuscript. This work was supported by KAKENHI ( 16H02627 , 15H01249 , and 16H06600 ); a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT); and the Japanese Initiative for Progress of Research on Infectious Disease for Global Epidemics (J-PRIDE) ( JP17fm0208101 and JP18fm0208101 ) from the Japan Agency for Medical Research and Development (AMED). Funding was also provided in part by the Science and Technology Research Partnership for Sustainable Development (SATREPS) ( JP18jm0110019 ), the Japan Initiative for Global Research Network on Infectious Diseases (J-GRID) ( JP18fm0108008 ), the Program for Leading Graduate Schools from MEXT , Japan, and the Intramural Research Program of the NIAID, NIH . Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2020",
month = jan,
day = "14",
doi = "10.1016/j.celrep.2019.12.042",
language = "English (US)",
volume = "30",
pages = "308--319.e5",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "2",
}