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一种新型单克隆抗体通过靶向纤维-2,有效地阻止了 4 型禽腺病毒的感染。

A novel monoclonal antibody efficiently blocks the infection of serotype 4 fowl adenovirus by targeting fiber-2.

机构信息

Key Laboratory of Jiangsu Preventive Veterinary Medicine, Key Laboratory for Avian Preventive Medicine, Ministry of Education, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, China.

Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China.

出版信息

Vet Res. 2018 Mar 9;49(1):29. doi: 10.1186/s13567-018-0525-y.

Abstract

A recent outbreak of hepatitis-hydropericardium syndrome caused by serotype 4 fowl adenovirus (FAdV-4) has resulted in significant economic losses to the poultry industry worldwide. However, little is known about the molecular pathogenesis of FAdV-4. In this study, a novel monoclonal antibody (mAb) targeting the fiber-2 protein of FAdV-4 was generated, mAb 3C2. Indirect immunofluorescence assay showed that mAb 3C2 neither reacted with serotype 8 fowl adenovirus (FAdV-8) nor reacted with the fiber-1 protein of FAdV-4; it specifically reacted with the fiber-2 protein of FAdV-4. Notably, mAb 3C2 could efficiently immunoprecipitate the fiber-2 protein in chicken liver cells either infected with FAdV-4 or transfected with pcDNA3.1-Fiber2. Moreover, mAb 3C2 demonstrated marked neutralizing activity against FAdV-4 and could efficiently inhibit the infection of FAdV-4 in vitro. Using truncated fiber-2 constructs, the epitope recognized by mAb 3C2 was determined to be located between amino acids 416-448 at the C-terminus of fiber-2. Our data not only provide a foundation for the establishment of a rapid fiber-2 peptide-based diagnostic assay for FAdV-4 but also highlight the critical role of the fiber-2 protein in mediating infection by FAdV-4. Furthermore, the epitope recognized by 3C2 might serve as a novel target for the development of a vaccine targeting FAdV-4.

摘要

最近由血清型 4 禽腺病毒(FAdV-4)引起的肝炎-心包积水综合征爆发给全球家禽业造成了巨大的经济损失。然而,关于 FAdV-4 的分子发病机制知之甚少。在这项研究中,我们制备了一种针对 FAdV-4 纤维-2 蛋白的新型单克隆抗体(mAb),即 mAb 3C2。间接免疫荧光试验表明,mAb 3C2 既不与血清型 8 禽腺病毒(FAdV-8)反应,也不与 FAdV-4 的纤维-1 蛋白反应,它特异性地与 FAdV-4 的纤维-2 蛋白反应。值得注意的是,mAb 3C2 可有效地免疫沉淀感染 FAdV-4 或转染 pcDNA3.1-Fiber2 的鸡肝细胞中的纤维-2 蛋白。此外,mAb 3C2 对 FAdV-4 表现出明显的中和活性,可有效地抑制 FAdV-4 的体外感染。利用截短的纤维-2 构建体,确定 mAb 3C2 识别的表位位于纤维-2 蛋白 C 末端的 416-448 位氨基酸之间。我们的数据不仅为建立基于纤维-2 肽的快速 FAdV-4 诊断检测方法奠定了基础,还强调了纤维-2 蛋白在介导 FAdV-4 感染中的关键作用。此外,3C2 识别的表位可能成为针对 FAdV-4 疫苗开发的新型靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0794/5845368/f87e9e2a408c/13567_2018_525_Fig1_HTML.jpg

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