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人类和禽流感病毒 HA 保守区的异嗜性表位可产生与肾脏组织结合的抗体。

The heterophilicic epitopes in conserved HA regions of human and avian influenza viruses can produce antibodies that bound to kidney tissue.

机构信息

Shaanxi Provincial People's Hospital, Xi'an, 710068, China; Shaanxi Engineering Research Center of Cell Immunology, Xi'an, 710068, China; Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Xi'an, 710068, China.

Shaanxi Provincial People's Hospital, Xi'an, 710068, China.

出版信息

Microb Pathog. 2023 Dec;185:106331. doi: 10.1016/j.micpath.2023.106331. Epub 2023 Sep 9.

Abstract

Influenza virus infection can cause kidney damage. However, the link between influenza infection and disease is still unclear. The purpose of this study was to analyze the relationship between heterophilic epitopes on H5N1 hemagglutinin (HA) and disease. The monoclonal antibody (mAb) against H5N1 was prepared, mAbs binding to human kidney tissue were screened, and the reactivities of mAbs with five different subtypes of influenza virus were detected. Design and synthesize the peptides according to the common amino acid sequence of these antigens, and analyze the distribution of the epitope on the crystal structure of HA. Immunological methods were used to detect whether the heterophilic epitopes could induce the production of antibodies that cross-react with kidney tissue. The results showed that H5-30 mA b binding to human kidney tissue recognized the heterophilic epitope 191-LVLWGIHHP-199 on the head of HA. The key amino acid were V192, L193, W194 and I196, which were highly conserved in human and avian influenza virus HA. The heterophilic epitope could induce mice to produce different mAbs binding to kidney tissue. Such heterophilic antibodies were also detected in the serum of the patients. It can provide materials for the mechanism of renal diseases caused by influenza virus infection.

摘要

流感病毒感染可导致肾脏损伤。然而,流感感染与疾病之间的联系仍不清楚。本研究旨在分析 H5N1 血凝素(HA)上的异嗜性表位与疾病之间的关系。制备了针对 H5N1 的单克隆抗体(mAb),筛选与人肾组织结合的 mAb,并检测 mAb 与五种不同亚型流感病毒的反应性。根据这些抗原的共有氨基酸序列设计并合成肽,并分析 HA 晶体结构上表位的分布。采用免疫学方法检测异嗜性表位是否能诱导产生与肾组织发生交叉反应的抗体。结果表明,与人肾组织结合的 H5-30 mAb 识别 HA 头部的异嗜性表位 191-LVLWGIHHP-199。关键氨基酸为 V192、L193、W194 和 I196,在人类和禽流感病毒 HA 中高度保守。异嗜性表位可诱导小鼠产生不同的与肾组织结合的 mAb。在患者的血清中也检测到了这种异嗜性抗体。它可为流感病毒感染引起肾脏疾病的机制提供材料。

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