Q221K mutation in VP2 drives antigenic shift of infectious bursal disease virus
IntroductionInfectious bursal disease (IBD) is a severe immunosuppressive disease caused by the infection of infectious bursal disease virus (IBDV) in chicken. Recently, an emerging mutant named novel variant IBDV (nVarIBDV) has rapidly spread in China and become a prevalent strain. However, little...
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2025-07-01
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| author | Haifeng Xiong Haifeng Xiong Haifeng Xiong Jiayan Wu Jiayan Wu Jiayan Wu Quan Xie Quan Xie Quan Xie Quan Xie Tuofan Li Tuofan Li Tuofan Li Tuofan Li Zhimin Wan Zhimin Wan Zhimin Wan Zhimin Wan Aijian Qin Aijian Qin Aijian Qin Aijian Qin Jianqiang Ye Jianqiang Ye Jianqiang Ye Jianqiang Ye Hongxia Shao Hongxia Shao Hongxia Shao Hongxia Shao |
| author_facet | Haifeng Xiong Haifeng Xiong Haifeng Xiong Jiayan Wu Jiayan Wu Jiayan Wu Quan Xie Quan Xie Quan Xie Quan Xie Tuofan Li Tuofan Li Tuofan Li Tuofan Li Zhimin Wan Zhimin Wan Zhimin Wan Zhimin Wan Aijian Qin Aijian Qin Aijian Qin Aijian Qin Jianqiang Ye Jianqiang Ye Jianqiang Ye Jianqiang Ye Hongxia Shao Hongxia Shao Hongxia Shao Hongxia Shao |
| author_sort | Haifeng Xiong |
| collection | DOAJ |
| description | IntroductionInfectious bursal disease (IBD) is a severe immunosuppressive disease caused by the infection of infectious bursal disease virus (IBDV) in chicken. Recently, an emerging mutant named novel variant IBDV (nVarIBDV) has rapidly spread in China and become a prevalent strain. However, little is known about the unique antigenic sites of nVarIBDV escaped from current IBDV vaccines.MethodsHere, the expressed hypervariable region (HVR) of VP2 (VP2-HVR) of nVarIBDV was used as an immunogen and a novel monoclonal antibody (mAb) against VP2 (mAb 5B5) was generated.ResultsImmunofluorescence assay (IFA) and ELISA demonstrated that mAb 5B5 specifically reacted with nVarIBDV and its VP2 protein, but not with classical IBDV (cIBDV), very virulent IBDV (vvIBDV), or attenuated IBDV (attIBDV) strains. Epitope mapping and site mutagenesis assay revealed that mAb 5B5 recognized the conformational epitope in peak A (212–224 aa) and heptapeptide (326–332 aa) regions, and identified residue 221K in VP2 as the key antigenic site, which is conserved exclusively in nVarIBDV strains. Notably, K221Q mutation in VP2 of nVarIBDV significantly altered the reaction profile for sera against vvIBDV or cIBDV. Neutralization assays revealed that mAb 5B5 could inhibit replication of an engineered attIBDV carrying 221K in Leghorn male hepatoma (LMH) cells. Structural analysis further found that 221K is surface-exposed and alters local electrostatic potential, possibly facilitating immune evasion.DiscussionAll these demonstrated that 221K is a unique antigenic site in VP2 of nVarIBDV associated with immune escape, providing novel insights into the antigenicity of nVarIBDV and novel targets for efficient diagnostics, vaccine design, and molecular surveillance of IBDV. |
| format | Article |
| id | doaj-art-4af110c6e4e04ad196fabf5be20e54f9 |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-4af110c6e4e04ad196fabf5be20e54f92025-08-20T03:17:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16003711600371Q221K mutation in VP2 drives antigenic shift of infectious bursal disease virusHaifeng Xiong0Haifeng Xiong1Haifeng Xiong2Jiayan Wu3Jiayan Wu4Jiayan Wu5Quan Xie6Quan Xie7Quan Xie8Quan Xie9Tuofan Li10Tuofan Li11Tuofan Li12Tuofan Li13Zhimin Wan14Zhimin Wan15Zhimin Wan16Zhimin Wan17Aijian Qin18Aijian Qin19Aijian Qin20Aijian Qin21Jianqiang Ye22Jianqiang Ye23Jianqiang Ye24Jianqiang Ye25Hongxia Shao26Hongxia Shao27Hongxia Shao28Hongxia Shao29Key Laboratory of Jiangsu Preventive Veterinary Medicine, Key Laboratory for Avian Preventive Medicine, Ministry of Education, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, ChinaJiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, ChinaKey Laboratory of Jiangsu Preventive Veterinary Medicine, Key Laboratory for Avian Preventive Medicine, Ministry of Education, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, ChinaJiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, ChinaKey Laboratory of Jiangsu Preventive Veterinary Medicine, Key Laboratory for Avian Preventive Medicine, Ministry of Education, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, ChinaJiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, ChinaInstitutes of Agricultural Science and Technology Development, Yangzhou University, Yangzhou, Jiangsu, ChinaKey Laboratory of Jiangsu Preventive Veterinary Medicine, Key Laboratory for Avian Preventive Medicine, Ministry of Education, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, ChinaJiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, ChinaInstitutes of Agricultural Science and Technology Development, Yangzhou University, Yangzhou, Jiangsu, ChinaKey Laboratory of Jiangsu Preventive Veterinary Medicine, Key Laboratory for Avian Preventive Medicine, Ministry of Education, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, ChinaJiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, ChinaInstitutes of Agricultural Science and Technology Development, Yangzhou University, Yangzhou, Jiangsu, ChinaKey Laboratory of Jiangsu Preventive Veterinary Medicine, Key Laboratory for Avian Preventive Medicine, Ministry of Education, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, ChinaJiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, ChinaInstitutes of Agricultural Science and Technology Development, Yangzhou University, Yangzhou, Jiangsu, ChinaKey Laboratory of Jiangsu Preventive Veterinary Medicine, Key Laboratory for Avian Preventive Medicine, Ministry of Education, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, ChinaJiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, ChinaInstitutes of Agricultural Science and Technology Development, Yangzhou University, Yangzhou, Jiangsu, ChinaKey Laboratory of Jiangsu Preventive Veterinary Medicine, Key Laboratory for Avian Preventive Medicine, Ministry of Education, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, ChinaJiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, ChinaJoint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu, ChinaInstitutes of Agricultural Science and Technology Development, Yangzhou University, Yangzhou, Jiangsu, ChinaIntroductionInfectious bursal disease (IBD) is a severe immunosuppressive disease caused by the infection of infectious bursal disease virus (IBDV) in chicken. Recently, an emerging mutant named novel variant IBDV (nVarIBDV) has rapidly spread in China and become a prevalent strain. However, little is known about the unique antigenic sites of nVarIBDV escaped from current IBDV vaccines.MethodsHere, the expressed hypervariable region (HVR) of VP2 (VP2-HVR) of nVarIBDV was used as an immunogen and a novel monoclonal antibody (mAb) against VP2 (mAb 5B5) was generated.ResultsImmunofluorescence assay (IFA) and ELISA demonstrated that mAb 5B5 specifically reacted with nVarIBDV and its VP2 protein, but not with classical IBDV (cIBDV), very virulent IBDV (vvIBDV), or attenuated IBDV (attIBDV) strains. Epitope mapping and site mutagenesis assay revealed that mAb 5B5 recognized the conformational epitope in peak A (212–224 aa) and heptapeptide (326–332 aa) regions, and identified residue 221K in VP2 as the key antigenic site, which is conserved exclusively in nVarIBDV strains. Notably, K221Q mutation in VP2 of nVarIBDV significantly altered the reaction profile for sera against vvIBDV or cIBDV. Neutralization assays revealed that mAb 5B5 could inhibit replication of an engineered attIBDV carrying 221K in Leghorn male hepatoma (LMH) cells. Structural analysis further found that 221K is surface-exposed and alters local electrostatic potential, possibly facilitating immune evasion.DiscussionAll these demonstrated that 221K is a unique antigenic site in VP2 of nVarIBDV associated with immune escape, providing novel insights into the antigenicity of nVarIBDV and novel targets for efficient diagnostics, vaccine design, and molecular surveillance of IBDV.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1600371/fullnVarIBDVVP2mAb221Kantigenicitydifferentiation |
| spellingShingle | Haifeng Xiong Haifeng Xiong Haifeng Xiong Jiayan Wu Jiayan Wu Jiayan Wu Quan Xie Quan Xie Quan Xie Quan Xie Tuofan Li Tuofan Li Tuofan Li Tuofan Li Zhimin Wan Zhimin Wan Zhimin Wan Zhimin Wan Aijian Qin Aijian Qin Aijian Qin Aijian Qin Jianqiang Ye Jianqiang Ye Jianqiang Ye Jianqiang Ye Hongxia Shao Hongxia Shao Hongxia Shao Hongxia Shao Q221K mutation in VP2 drives antigenic shift of infectious bursal disease virus Frontiers in Immunology nVarIBDV VP2 mAb 221K antigenicity differentiation |
| title | Q221K mutation in VP2 drives antigenic shift of infectious bursal disease virus |
| title_full | Q221K mutation in VP2 drives antigenic shift of infectious bursal disease virus |
| title_fullStr | Q221K mutation in VP2 drives antigenic shift of infectious bursal disease virus |
| title_full_unstemmed | Q221K mutation in VP2 drives antigenic shift of infectious bursal disease virus |
| title_short | Q221K mutation in VP2 drives antigenic shift of infectious bursal disease virus |
| title_sort | q221k mutation in vp2 drives antigenic shift of infectious bursal disease virus |
| topic | nVarIBDV VP2 mAb 221K antigenicity differentiation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1600371/full |
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