Niemann-Pick C1 Heterogeneity of Bat Cells Controls Filovirus Tropism

Yoshihiro Takadate; Tatsunari Kondoh; Manabu Igarashi; Junki Maruyama; Rashid Manzoor; Hirohito Ogawa; Masahiro Kajihara; Wakako Furuyama; Masahiro Sato; Hiroko Miyamoto; Reiko Yoshida; Terence E Hill; Alexander N Freiberg; Heinz Feldmann; Andrea Marzi; Ayato Takada

doi:10.1016/j.celrep.2019.12.042

Niemann-Pick C1 Heterogeneity of Bat Cells Controls Filovirus Tropism

Cell Rep. 2020 Jan 14;30(2):308-319.e5. doi: 10.1016/j.celrep.2019.12.042.

Authors

Yoshihiro Takadate¹, Tatsunari Kondoh¹, Manabu Igarashi², Junki Maruyama¹, Rashid Manzoor¹, Hirohito Ogawa³, Masahiro Kajihara¹, Wakako Furuyama⁴, Masahiro Sato¹, Hiroko Miyamoto¹, Reiko Yoshida¹, Terence E Hill⁵, Alexander N Freiberg⁵, Heinz Feldmann⁴, Andrea Marzi⁴, Ayato Takada⁶

Affiliations

¹ Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
² Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan; Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo 001-0020, Japan.
³ Hokudai Center for Zoonosis Control in Zambia, School of Veterinary Medicine, University of Zambia, Lusaka 10101, Zambia; Department of Disease Control, School of Veterinary Medicine, University of Zambia, Lusaka 10101, Zambia.
⁴ Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT 59840, USA.
⁵ Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555, USA.
⁶ Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan; Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo 001-0020, Japan; Department of Disease Control, School of Veterinary Medicine, University of Zambia, Lusaka 10101, Zambia. Electronic address: atakada@czc.hokudai.ac.jp.

PMID: 31940478
DOI: 10.1016/j.celrep.2019.12.042

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.

Keywords: Ebola virus; Marburg virus; Niemann-Pick C1; bat; filovirus; glycoprotein; host range; natural host; receptor; virus-host interaction.

Publication types

Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Chiroptera
Filoviridae / genetics*
Humans
Models, Molecular
Niemann-Pick C1 Protein / metabolism*
Tropism / genetics*

Substances

Niemann-Pick C1 Protein