Structure and immune recognition of the porcine epidemic diarrhea virus spike protein.

Structure and immune recognition of the porcine epidemic diarrhea virus spike protein.
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DOI:
10.1016/j.str.2020.12.003
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发表时间:
2021-04-01
期刊:
Structure (London, England : 1993)
影响因子:
--
通讯作者:
Ward AB
Ward AB
中科院分区:
其他
文献类型:
--
作者:
Kirchdoerfer RN;Bhandari M;Martini O;Sewall LM;Bangaru S;Yoon KJ;Ward AB

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猪流行性腹泻病毒(PEDV)是一种引起猪严重发病和死亡的冠状病毒。作为病毒嗜性和进入的关键决定因素,PEDV刺突蛋白是宿主抗体应答的关键靶标,并且是基于蛋白质的疫苗免疫原的良好候选物。我们使用电子显微镜来评估PEDV刺突结构,以及猪多克隆抗体对病毒感染的应答。PEDV刺突的结构揭示了与HuCoV-NL 63类似的构型。几种PEDV蛋白质-蛋白质界面由非蛋白质组分介导,包括Asn 264处的聚糖和两个结合的棕榈油酸分子。对PEDV感染的多克隆抗体应答显示S1区的表位占优势。这种结构和免疫表征提供了对冠状病毒刺突稳定性决定因素的见解,并探索了病毒刺突蛋白的免疫景观。Kirchdoerfer等人使用猪流行性腹泻病毒刺突胞外域的冷冻电子显微镜来鉴定蛋白质-蛋白质界面中的聚糖和脂肪酸,并描绘猪对感染的免疫应答所靶向的表位。
Porcine epidemic diarrhea virus (PEDV) is an alphacoronavirus responsible for significant morbidity and mortality in pigs. A key determinant of viral tropism and entry, the PEDV spike protein is a key target for the host antibody response and a good candidate for a protein-based vaccine immunogen. We used electron microscopy to evaluate the PEDV spike structure, as well as pig polyclonal antibody responses to viral infection. The structure of the PEDV spike reveals a configuration similar to that of HuCoV-NL63. Several PEDV protein-protein interfaces are mediated by non-protein components, including a glycan at Asn264 and two bound palmitoleic acid molecules. The polyclonal antibody response to PEDV infection shows a dominance of epitopes in the S1 region. This structural and immune characterization provides insights into coronavirus spike stability determinants and explores the immune landscape of viral spike proteins. Kirchdoerfer et al. use cryoelectron microscopy of the porcine epidemic diarrhea virus spike ectodomain to identify glycans and fatty acids in protein-protein interfaces and delineate epitopes targeted by the pig immune response to infection.
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