Journal
MICROORGANISMS
Volume 8, Issue 10, Pages -Publisher
MDPI
DOI: 10.3390/microorganisms8101530
Keywords
filovirus; lloviu virus; Miniopterus sp; bat; insectivorous bat; host range; Niemann– Pick C1; glycoprotein
Categories
Funding
- Japan Society for the Promotion of Science (JSPS) [15H01249, 16H06600, 19J10604]
- Japanese Initiative for Progress of Research on Infectious Disease for Global Epidemics (J-PRIDE) from the Japan Agency for Medical Research and Development (AMED) [JP18fm0208101, JP18fm0208001]
- Science and Technology Research Partnership for Sustainable Development (SATREPS) [JP19jm0110019]
- Japan Initiative for Global Research Network on Infectious Diseases (J-GRID) [JP19fm0108008]
- KAKENHI [19J10604]
- Grants-in-Aid for Scientific Research [19J10604, 15H01249, 16H06600] Funding Source: KAKEN
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Lloviu virus (LLOV), a bat-derived filovirus that is phylogenetically distinct from human pathogenic filoviruses such as Ebola virus (EBOV) and Marburg virus (MARV), was discovered in Europe. However, since infectious LLOV has never been isolated, the biological properties of this virus remain poorly understood. We found that vesicular stomatitis virus (VSV) pseudotyped with the glycoprotein (GP) of LLOV (VSV-LLOV) showed higher infectivity in one bat (Miniopterus sp.)-derived cell line than in the other bat-derived cell lines tested, which was distinct from the tropism of VSV pseudotyped with EBOV (VSV-EBOV) and MARV GPs. We then focused on the interaction between GP and Niemann-Pick C1 (NPC1) protein, one of the cellular receptors of filoviruses. We introduced the Miniopterus bat and human NPC1 genes into NPC1-knockout Vero E6 cells and their susceptibilities to the viruses were compared. The cell line expressing the bat NPC1 showed higher susceptibility to VSV-LLOV than that expressing human NPC1, whereas the opposite preference was seen for VSV-EBOV. Using a site-directed mutagenesis approach, amino acid residues involved in the differential tropism were identified in the NPC1 and GP molecules. Our results suggest that the interaction between GP and NPC1 is an important factor in the tropism of LLOV to a particular bat species.
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