包膜糖蛋白 I 的 N-糖基化对鸭瘟病毒的增殖和毒力至关重要。

IF 3.7 1区 农林科学 Q1 VETERINARY SCIENCES Veterinary Research Pub Date : 2024-10-26 DOI:10.1186/s13567-024-01398-4
Yaru Ning, Mingshu Wang, Anchun Cheng, Qiao Yang, Bin Tian, Xumin Ou, Di Sun, Yu He, Zhen Wu, Xinxin Zhao, Shaqiu Zhang, Ying Wu, Juan Huang, Yanling Yu, Ling Zhang, Renyong Jia, Mafeng Liu, Dekang Zhu, Shun Chen
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引用次数: 0

摘要

鸭瘟病毒(DPV)会导致高致病性鸭瘟,而包膜糖蛋白 I(gI)作为关键毒力基因之一,其关键毒力位点尚未通过筛选确定。本研究利用反向遗传学技术,专门针对 DPV 基因组中的 gI。我们设计并构建了四个具有 gI N-糖基化位点突变的 DPV 突变体,并成功地挽救了这些突变株。我们的结果证实,gI的三个天冬酰胺残基(N69、N78和N265)是N-糖基化位点,Western印迹分析证实,每个预测的N-糖基化位点的糖基化都受到了影响。gI 的去糖基化导致蛋白质错误折叠,随后滞留在内质网(ER)中。随后脱糖的 gI 在 gE 的相互作用下被带入高尔基体(GM130)。与亲本病毒相比,变异病毒的细胞间传播能力降低了 66.3%。在鸭体内,gI 的脱糖基化大大降低了 DPV 在体内的复制,从而削弱了 DPV 的毒力。这项研究首次成功地通过N-糖基化位点的特异性突变创建了弱DPV病毒株。这些发现为人们了解 DPV 的致病机理提供了基础,并为开发针对该疾病的减毒活疫苗奠定了基础。
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N-glycosylation of the envelope glycoprotein I is essential for the proliferation and virulence of the duck plague virus.

Duck plague virus (DPV) causes the highly pathogenic duck plague, and the envelope glycoprotein I (gI), as one of the key virulence genes, has not yet had its critical virulence sites identified through screening. This study used reverse genetics technology to target the gI, specifically within the DPV genome. Four DPV mutants with gI N-glycosylation site mutations were designed and constructed, and these mutant strains were successfully rescued. Our results confirmed that three asparagine residues of gI (N69, N78, and N265) are N-glycosylation sites, and western blot analysis substantiated that glycosylation at each predicted N-glycosylation site was compromised. The deglycosylation of gI leads to the protein misfolding and subsequent retention in the endoplasmic reticulum (ER). The subsequent deglycosylated gI is carried into the Golgi apparatus (GM130) in the interaction of gE. Compared to the parental virus, the mutated virus shows a 66.3% reduction in intercellular transmission capability. In ducks, the deglycosylation of gI significantly reduces DPV replication in vivo, thereby weakening the virulence of DPV. This study represents the first successful creation of a weak DPV virus strain by specific mutation at the N-glycosylation site. The findings provide a foundational understanding of DPV pathogenesis and form the basis for developing live attenuated vaccines against the disease.

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来源期刊
Veterinary Research
Veterinary Research 农林科学-兽医学
CiteScore
7.00
自引率
4.50%
发文量
92
审稿时长
3 months
期刊介绍: Veterinary Research is an open access journal that publishes high quality and novel research and review articles focusing on all aspects of infectious diseases and host-pathogen interaction in animals.
期刊最新文献
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