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

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)308-319.e5
JournalCell Reports
Volume30
Issue number2
DOIs
StatePublished - Jan 14 2020

Keywords

  • Ebola virus
  • Marburg virus
  • Niemann-Pick C1
  • bat
  • filovirus
  • glycoprotein
  • host range
  • natural host
  • receptor
  • virus-host interaction

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Niemann-Pick C1 Heterogeneity of Bat Cells Controls Filovirus Tropism'. Together they form a unique fingerprint.

  • Cite this

    Takadate, Y., Kondoh, T., Igarashi, M., Maruyama, J., Manzoor, R., Ogawa, H., Kajihara, M., Furuyama, W., Sato, M., Miyamoto, H., Yoshida, R., Hill, T. E., Freiberg, A. N., Feldmann, H., Marzi, A., & Takada, A. (2020). Niemann-Pick C1 Heterogeneity of Bat Cells Controls Filovirus Tropism. Cell Reports, 30(2), 308-319.e5. https://doi.org/10.1016/j.celrep.2019.12.042