Infectious bursal disease virus(IBDV)causes a highly contagious immunosuppressive disease in chickens,resulting in significant economic losses.The very virulent IBDV strain(vvIBDV)causes high mortality and cannot adapt to cell culture.In contrast,attenuated strains of IBDV are nonpathogenic to chickens and can replicate in cell culture.Although the crystal structure of T=1 subviral particles(SVP)has been reported,the structures of intact IBDV virions with different virulences remain elusive.Here,we deter-mined the cryo-electron microscopy(cryo-EM)structures of the vvIBDV Gx strain and its attenuated IBDV strain Gt at resolutions of 3.3 ? and 3.2 ?,respectively.Compared with the structure of T=1 SVP,IBDV contains several conserved structural elements unique to the T=13 virion.Notably,the N-terminus of VP2,which is disordered in the SVP,interacts with the SF strand of VP2 from its neighboring trimer,completing the β-sheet of the S domain.This interaction helps to form a contact network by teth-ering the adjacent VP2 trimers and contributes to the assembly and stability of the IBDV virion.Structural comparison of the Gx and Gt strains indicates that H253 and T284 in the VP2 P domain of Gt,in contrast to Gx,form a hydrogen bond with a positively charged surface.This suggests that the combined muta-tions Q253H/A284T and the associated structural electrostatic features of the attenuated Gt strain may contribute to adaptation to cell culture.Furthermore,a negatively charged groove in VP2,containing an integrin binding IDA motif that is critical for virus attachment,was speculated to play a functional role in the entry of IBDV.

Keyan Bao;Xiaole Qi;Yan Li;Minqing Gong;Xiaomei Wang;Ping Zhu

National Laboratory of Biomacromolecules,CAS Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China;Avian Immunosuppressive Diseases Division,State Key Laboratory of Veterinary Biotechnology,Harbin Veterinary Research Institute,Chinese Academy of Agricultural Sciences,Harbin 150069,China;OIE Reference Laboratory for Infectious Bursal Disease,Harbin Veterinary Research Institute,Chinese Academy of Agricultural Sciences,Harbin 150069,China;College of Life Sciences,University of Chinese Academy of Sciences,Beijing 100049,China

科学通报（英文版）

[1]Keyan Bao;Xiaole Qi;Yan Li;Minqing Gong;Xiaomei Wang;Ping Zhu-.Cryo-EM structures of infectious bursal disease viruses with different virulences provide insights into their assembly and invasion)[J].科学通报（英文版）,2022(06):646-654

virulences,vvIBDV,nonpathogenic,subviral,teth,H253,T284,Q253H,A284T

Cryo,EM,structures,infectious,bursal,disease,viruses,different,provide,insights,into,their,assembly,invasion,Infectious,causes,highly,contagious,immunosuppressive,chickens,resulting,significant,economic,losses,very,virulent,mortality,cannot,cell,culture,contrast,attenuated,strains,replicate,Although,crystal,particles,SVP,has,been,reported,intact,virions,remain,elusive,Here,we,deter,mined,cryo,electron,microscopy,Gx,its,Gt,resolutions,respectively,Compared,contains,several,conserved,structural,elements,unique,Notably,terminus,VP2,which,disordered,interacts,SF,strand,from,neighboring,completing,sheet,domain,This,interaction,helps,form,contact,network,by,ering,adjacent,trimers,contributes,stability,Structural,comparison,indicates,that,hydrogen,bond,positively,charged,surface,suggests,combined,muta,associated,electrostatic,features,may,adaptation,Furthermore,negatively,groove,containing,integrin,binding,IDA,motif,critical,attachment,was,speculated,play,functional,role,entry

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