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

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.

Cell reports

30

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319

10.1016/j.celrep.2019.12.042

https://doi.org/10.1016/j.celrep.2019.12.042
https://www.ncbi.nlm.nih.gov/pubmed/31940478