Niemann-Pick C1 Heterogeneity of Bat Cells Controls Filovirus Tropism

• Published in: Cell reports (Cambridge) Vol. 30; no. 2; pp. 308 - 319.e5
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.01.2020; Elsevier
• Subjects: Amino Acid Sequence; Animals; bat; Chiroptera; Ebola virus; Filoviridae - genetics; filovirus; glycoprotein; host range; Humans; Marburg virus; Models, Molecular; natural host; Niemann-Pick C1; Niemann-Pick C1 Protein - metabolism; receptor; Tropism - genetics; virus-host interaction; Ebola virus; virus-host interaction; natural host; receptor; Niemann-Pick C1; Marburg virus; bat; glycoprotein; filovirus; host range
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2019.12.042

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. [Display omitted] •Some bat cell lines show differential susceptibilities to Ebola and Marburg viruses•Distinctive amino acid sequences exist in the filovirus receptor of some bats•Receptor heterogeneity in bat species controls their susceptibility to filoviruses•Receptor preference is important for differential filovirus tropism to bat cells 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.