Abstract:
Infectious bursa disease (IBD) is an acute, highly contactable, lethal, immunosuppressive infectious disease caused by the Infectious bursa disease virus (IBDV). Currently, the emerged novel variant IBDV (nVarIBDV) and the sustainedly prevalent very virulent IBDV (vvIBDV) are the two most prevalent strains of IBDV in China. The antigenic properties of the two prevalent strains differed significantly, which led to the escape of nVarIBDV from the immune protection provided by the existing vvIBDV vaccine. However, the molecular basis of the nVarIBDV immune escape remains unclear. In this study, we demonstrated, for the first time, that residues 252, 254, and 256 in the PDE of VP2 are involved in the immune escape of the emerging nVarIBDV. Firstly, the IFA-mediated antigen-antibody affinity assay showed that PBC and PDE of VP2 could affect the affinity of vvIBDV antiserum to VP2, of which PDE was more significant. The key amino acids of PDE influencing the antigen-antibody affinity were also identified, with G254N being the most significant, followed by V252I and I256V. Then the mutated virus with point or combined mutations was rescued by reverse genetics. it was further demonstrated that mutations of V252I, G254N, and I256V in PDE could individually or collaboratively reduce antigen-antibody affinity and interfere with antiserum neutralization, with G254N being the most significant. This study revealed the reasons for the widespread prevalence of nVarIBDV in immunized chicken flocks and provided innovative ideas for designing novel vaccines that match the antigen of the epidemic strain.
摘要:
传染性法氏囊病(IBD)是一种急性,高度可联系,致命的,由传染性法氏囊病病毒(IBDV)引起的免疫抑制性传染病。目前,出现的新变种IBDV(nVarIBDV)和持续流行的剧毒IBDV(vvIBDV)是中国最流行的两种IBDV菌株。两种流行菌株的抗原特性差异显着,这导致nVarIBDV从现有的vvIBDV疫苗提供的免疫保护中逃脱。然而,nVarIBDV免疫逃逸的分子基础尚不清楚。在这项研究中,我们展示了,第一次,VP2的PDE中的残基252、254和256参与新出现的nVarIBDV的免疫逃逸。首先,IFA介导的抗原抗体亲和力分析表明,VP2的PBC和PDE可以影响vvIBDV抗血清对VP2的亲和力,其中PDE更显著。还鉴定了影响抗原-抗体亲和力的PDE的关键氨基酸。G254N是最重要的,其次是V252I和I256V。然后通过反向遗传学拯救具有点或组合突变的突变病毒。进一步证明了V252I的突变,G254N,PDE中的I256V和I256V可以单独或协同降低抗原抗体亲和力并干扰抗血清中和,G254N是最重要的。这项研究揭示了nVarIBDV在免疫鸡群中广泛流行的原因,并为设计与流行株抗原相匹配的新型疫苗提供了创新思路。