Ebolaviruses,such as the highly pathogenic Ebola virus(EBOV),belong to the family Filoviridae and have caused out-breaks of severe and fatal hemorrhagic fever over the past years.Bombali virus(BOMV)is a newly discover...Ebolaviruses,such as the highly pathogenic Ebola virus(EBOV),belong to the family Filoviridae and have caused out-breaks of severe and fatal hemorrhagic fever over the past years.Bombali virus(BOMV)is a newly discovered ebolavirus from bats with unknown potential to infect humans.For most ebolaviruses,the interaction between viral glycoprotein(GP)and host receptor Niemann-Pick C1(NPC1)is crucial for viral entry and determines host tropism.Here,we analyzed the BOMV GP-mediated virus entry into human cells using our recently developed EBOV transcription-and replication-competent virus-like particle(trVLP)system.We demonstrated that while BOMV GP can be efficiently incorporated into trVLPs,it is inefficient in mediating trVLP entry into human cells.However,BOMV GP-mediated virus entry into human cells can be significantly enhanced by a few mutations in the NPC1-binding domain of GP.Furthermore,we showed that these mutations increase the binding of BOMV-GP to human NPC1.In summary,our results suggested that although wild-type BOMV does not efficiently infect human cells,the emergence of mutations in viral GP may boost its ability to spill over to humans,highlighting the importance of monitoring BOMV GP evolution in preventing potential BOMV spillover events.展开更多
基金supported by the grants from Key Research and Development Program,Ministry of Science and Technology of China(2022YFC2303300,2021YFC2300204)Shanghai Municipal Science and Technology Major Project(ZD2021CY001)+3 种基金Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29010205)Shanghai International Science and Technology Cooperation Program(21430713900)Program of Shanghai Academic/Technology Research Leader(22XD1403800)to J.Z.Advanced Customer Cultivation Project of Wuhan National Biosafety Laboratory,Chinese Academy of Sciences to J.Z.and H.Y.
文摘Ebolaviruses,such as the highly pathogenic Ebola virus(EBOV),belong to the family Filoviridae and have caused out-breaks of severe and fatal hemorrhagic fever over the past years.Bombali virus(BOMV)is a newly discovered ebolavirus from bats with unknown potential to infect humans.For most ebolaviruses,the interaction between viral glycoprotein(GP)and host receptor Niemann-Pick C1(NPC1)is crucial for viral entry and determines host tropism.Here,we analyzed the BOMV GP-mediated virus entry into human cells using our recently developed EBOV transcription-and replication-competent virus-like particle(trVLP)system.We demonstrated that while BOMV GP can be efficiently incorporated into trVLPs,it is inefficient in mediating trVLP entry into human cells.However,BOMV GP-mediated virus entry into human cells can be significantly enhanced by a few mutations in the NPC1-binding domain of GP.Furthermore,we showed that these mutations increase the binding of BOMV-GP to human NPC1.In summary,our results suggested that although wild-type BOMV does not efficiently infect human cells,the emergence of mutations in viral GP may boost its ability to spill over to humans,highlighting the importance of monitoring BOMV GP evolution in preventing potential BOMV spillover events.
