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

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.

Original languageEnglish
Pages (from-to)308-319.e5
JournalCell Reports
Volume30
Issue number2
DOIs
Publication statusPublished - Jan 14 2020
Externally publishedYes

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Tropism
Viruses
Marburgvirus
Ebolavirus
Viral Tropism
Amino Acids
Cell Line
Host Specificity
Cells
Amino Acid Sequence
Fruit
Glycoproteins
Fruits
Proteins

Cite this

Takadate, Y., Kondoh, T., Igarashi, M., Maruyama, J., Manzoor, R., Ogawa, H., ... 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

Niemann-Pick C1 Heterogeneity of Bat Cells Controls Filovirus Tropism. / Takadate, Yoshihiro; Kondoh, Tatsunari; Igarashi, Manabu; Maruyama, Junki; Manzoor, Rashid; Ogawa, Hirohito; Kajihara, Masahiro; Furuyama, Wakako; Sato, Masahiro; Miyamoto, Hiroko; Yoshida, Reiko; Hill, Terence E; Freiberg, Alexander N; Feldmann, Heinz; Marzi, Andrea; Takada, Ayato.

In: Cell Reports, Vol. 30, No. 2, 14.01.2020, p. 308-319.e5.

Research output: Contribution to journalArticle

Takadate, Y, Kondoh, T, Igarashi, M, Maruyama, J, Manzoor, R, Ogawa, H, Kajihara, M, Furuyama, W, Sato, M, Miyamoto, H, Yoshida, R, Hill, TE, Freiberg, AN, Feldmann, H, Marzi, A & Takada, A 2020, 'Niemann-Pick C1 Heterogeneity of Bat Cells Controls Filovirus Tropism', Cell Reports, vol. 30, no. 2, pp. 308-319.e5. https://doi.org/10.1016/j.celrep.2019.12.042
Takadate Y, Kondoh T, Igarashi M, Maruyama J, Manzoor R, Ogawa H et al. Niemann-Pick C1 Heterogeneity of Bat Cells Controls Filovirus Tropism. Cell Reports. 2020 Jan 14;30(2):308-319.e5. https://doi.org/10.1016/j.celrep.2019.12.042
Takadate, Yoshihiro ; Kondoh, Tatsunari ; Igarashi, Manabu ; Maruyama, Junki ; Manzoor, Rashid ; Ogawa, Hirohito ; Kajihara, Masahiro ; Furuyama, Wakako ; Sato, Masahiro ; Miyamoto, Hiroko ; Yoshida, Reiko ; Hill, Terence E ; Freiberg, Alexander N ; Feldmann, Heinz ; Marzi, Andrea ; Takada, Ayato. / Niemann-Pick C1 Heterogeneity of Bat Cells Controls Filovirus Tropism. In: Cell Reports. 2020 ; Vol. 30, No. 2. pp. 308-319.e5.
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AU - Manzoor, Rashid

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N2 - 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.

AB - 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.

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