Institute for Poultry Science and Health, Guangxi University, Nanning 530005, China.
School of Marine Sciences and Biotechnology, Guangxi University for Nationalities, Nanning 530006, China.
Viruses. 2021 Jan 14;13(1):107. doi: 10.3390/v13010107.
Infectious Bursal Disease Virus (IBDV) has haunted the poultry industry with severe, prolonged immunosuppression of chickens when infected at an early age and can easily lead to other secondary infections. Understanding the pathogenic mechanisms could lead to effective prevention and control of Infectious Bursal Disease (IBD). Evidence suggests that the N-terminal domain of polymerase in segment B plays an important role, but it is not clear which part or residual is crucial for the pathogenicity. Using a reverse genetics technique, a molecular clone (rNN1172) of the parental vvIBDV strain NN1172 was generated, and its pathogenicity was found to be the same as the parental virus. Then, three recombinant chimeric viruses were rescued based on the rNN1172 and substituted with the counterparts in the N-terminal domain of the attenuated vaccine strain B87: the rNN1172-B87VP1a (substituting the full region of the 1-167 aa residuals), the rNN1172-B87VP1a∆4 (substituting the region of the 5-167 aa residuals), and the rNN1172-VP1∆4 (one single aa residual substitution V4I), to better explore the role of the N-terminal domain of polymerase on the viral pathogenicity. Interestingly, all these substitutions played different roles in the viral pathogenicity: the mortality of the rNN1172-B87VP1a-challenged chickens was significantly reduced from 30% to 0%. No obvious lesion was found in the histopathological examination, and the lowest viral genome copy number was also detected in the bursa when compared to the parental and two other recombinant viruses. The mortalities caused by rNN1172-B87VP1a∆4 and rNN1172-B87VP1∆4, respectively, were all reduced to 10% and had a delayed onset of death. Our results also revealed that the pathogenicity of the IBDV was consistent with the viral replication efficiency in vivo (bursae). This study demonstrated that the full region of the N-terminal of polymerase plays an important role in viral replication and pathogenicity, but the substitutions of its partial region or a single residual do not completely lead to the virus attenuation to Three-Yellow chickens, although that significantly reduces its pathogenicity.
传染性腔上囊炎病毒（IBDV）对雏鸡造成严重、持久的免疫抑制，当雏鸡在早期感染时，很容易导致其他继发感染。了解其发病机制可以有效地预防和控制传染性腔上囊炎（IBD）。有证据表明，B 片段聚合酶的 N 端结构域在病毒复制中起着重要作用，但尚不清楚哪个部分或残基对其致病性至关重要。本研究利用反向遗传学技术，构建了亲本 vvIBDV 株 NN1172 的分子克隆（rNN1172），发现其致病性与亲本病毒相同。然后，基于 rNN1172 构建了三个嵌合重组病毒，并分别用弱毒疫苗株 B87 的 N 端结构域的对应物替换：rNN1172-B87VP1a（替换全长 1-167 aa 残基）、rNN1172-B87VP1a∆4（替换 5-167 aa 残基区域）和 rNN1172-VP1∆4（单个 aa 残基替换 V4I），以更好地探讨聚合酶 N 端结构域对病毒致病性的作用。有趣的是，这些替换在病毒致病性中发挥了不同的作用：rNN1172-B87VP1a 攻毒组雏鸡的死亡率从 30%显著降低至 0%。组织病理学检查未见明显病变，与亲本病毒和另外两个重组病毒相比，该病毒在腔上囊中检测到的病毒基因组拷贝数最低。rNN1172-B87VP1a∆4 和 rNN1172-B87VP1∆4 攻毒组的死亡率分别降低至 10%，且死亡时间延迟。我们的研究结果还表明，IBDV 的致病性与体内（腔上囊）病毒复制效率一致。本研究表明，聚合酶 N 端全长在病毒复制和致病性中起着重要作用，但部分区域或单个残基的替换并不能完全导致病毒对三黄鸡的毒力减弱，尽管其致病性显著降低。
