Receptor-Mediated Host Cell Preference of a Bat-Derived Filovirus, Lloviu Virus.

Hiroko Miyamoto,Yurie Kida,Yoshihiro Takadate,Tatsunari Kondoh,Manabu Igarashi,Rashid Manzoor,Junki Maruyama,Hirohito Ogawa,Ayato Takada,Masahiro Kajihara,Takeshi Saito

doi:10.3390/microorganisms8101530

Hiroko Miyamoto, Yurie Kida + Show 9 more

Open Access

https://doi.org/10.3390/microorganisms8101530

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Journal: Microorganisms	Publication Date: Oct 5, 2020
Citations: 10	License type: CC BY 4.0

Affiliation: Hokkaido University, University of Zambia

Abstract

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.

Highlights

Ebola virus (EBOV) and Marburg virus (MARV), belonging to the genera Ebolavirus and Marburgvirus, respectively, of the family Filoviridae, cause severe hemorrhagic fever in humans and nonhuman primates [1,2]
Using replication-incompetent vesicular stomatitis virus (VSV) pseudotyped with GPs of EBOV, MARV, and Lloviu virus (LLOV), we investigated GP-dependent tropism, which is the primary determinant for cell susceptibility to filoviruses
We found that SuBK12-08, a cell line derived from Miniopterus sp., showed higher susceptibility to VSV–LLOV than to VSV–EBOV and –MARV, cell lines derived from other bat species, including two insectivorous bat species, did not show such preferential susceptibility to VSV–LLOV

Summary

Introduction

Ebola virus (EBOV) and Marburg virus (MARV), belonging to the genera Ebolavirus and Marburgvirus, respectively, of the family Filoviridae, cause severe hemorrhagic fever in humans and nonhuman primates [1,2]. While the ecology of EBOV and MARV is largely unknown, some species of fruit bats are suspected to be natural reservoirs of these viruses [3,4,5,6,7]. In 2002, a novel filovirus, Lloviu virus (LLOV), phylogenetically distinct from the viruses in the genera Ebolavirus and Marburgvirus, was discovered in carcasses of insectivorous bats (Schreiber’s bent-winged bat: Miniopterus schreibersii) in Spain [8] and this virus was designated a new filovirus member belonging to the genus Cuevavirus [2,8]. The frequent detection of filoviruses in bats suggests that this animal is closely related to the ecology of filoviruses

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