Comparison of the biological properties of bat-derived filovirus envelope glycoproteins

Although some filoviruses, such as Ebola virus (EBOV) and Marburg virus (MARV), are highly pathogenic in humans, novel filoviruses, including Lloviu virus (LLOV), Bombali virus (BOMV), Mengla virus (MLAV), and Dehong virus (DEHV), whose biological properties are poorly understood, have been found in bats. In this study, we characterized the envelope glycoproteins (GPs) of these bat-derived filoviruses (BatFiloVs). We first confirmed that virus-like particles consisting of their GPs, nucleoproteins, and matrix proteins were filamentous. Interestingly, although BatFiloVs were serologically distinct, some previously established monoclonal antibodies (MAbs) (e.g., 6D6) successfully neutralized vesicular stomatitis Indiana viruses pseudotyped with LLOV, BOMV, or DEHV GPs. The pseudotyped viruses bearing BatFiloV GPs utilized human TIM-1 and C-type lectins for entry into cells, although the efficiency tended to be lower than for EBOV and/or MARV GP-pseudotyped viruses. These viruses broadly infected cultured cells derived from various animal species, including humans and bats. However, viruses pseudotyped with DEHV and MARV GPs failed to infect the Yaeyama flying fox cell line, whereas the other pseudotyped viruses infected this cell line. Interestingly, the virus bearing BOMV GP showed the greatest ability to infect cell lines derived from Angolan free-tailed bats, the only known host species of BOMV. We identified unique amino acid residues at the interface between GP and its receptor (i.e., Niemann-Pick C1), which might explain these differences. Our results suggest that the biological properties of filovirus GPs are generally consistent with their phylogenetic relationship and that BatFiloVs may have differential pathogenicity and host range restriction.IMPORTANCEFiloviruses, such as EBOV and MARV, are known to cause severe hemorrhagic fever in humans and nonhuman primates. With the recent advancements in next-generation sequencing, novel filoviruses have been detected in bats. However, their pathogenicity and host tropism remain largely unknown. Here, we focus on the filovirus spike protein GP, which plays a crucial role in the viral lifecycle, and discuss the biological properties of BatFiloVs. We studied the primary structures of GPs, virus particle morphology, antigenic differences of GPs, neutralizing capacities of anti-EBOV and -MARV GP MAbs, usage of some attachment factors during the entry into cells, and GP-mediated cellular tropism. The present study provides fundamental information for understanding the BatFiloV ecology, host ranges, and potential risks as zoonotic pathogens for humans. This knowledge will guide public health interventions to prevent virus spillovers and the development of surveillance strategies and specific countermeasures.