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针对人鼻病毒 A、B 和 C 种的病毒衣壳蛋白 1(VP1)抗原的特异性和交叉反应性 IgG1 抗体结合。

Species-specific and cross-reactive IgG1 antibody binding to viral capsid protein 1 (VP1) antigens of human rhinovirus species A, B and C.

机构信息

Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Australia.

出版信息

PLoS One. 2013 Aug 7;8(8):e70552. doi: 10.1371/journal.pone.0070552. eCollection 2013.

Abstract

BACKGROUND

Human rhinoviruses (HRV) are associated with upper and lower respiratory illnesses, including severe infections causing hospitalization in both children and adults. Although the clinical significance of HRV infections is now well established, no detailed investigation of the immune response against HRV has been performed. The purpose of this study was to assess the IgG1 antibody response to the three known HRV species, HRV-A, -B and -C in healthy subjects.

METHODS

Recombinant polypeptides of viral capsid protein 1 (VP1) from two genotypes of HRV-A, -B and -C were expressed as glutathione S-transferase (GST) fusion proteins and purified by affinity and then size exclusion chromatography. The presence of secondary structures similar to the natural antigens was verified by circular dichroism analysis. Total and species-specific IgG1 measurements were quantitated by immunoassays and immunoabsorption using sera from 63 healthy adults.

RESULTS

Most adult sera reacted with the HRV VP1 antigens, at high titres. As expected, strong cross-reactivity between HRV genotypes of the same species was found. A high degree of cross-reactivity between different HRV species was also evident, particularly between HRV-A and HRV-C. Immunoabsorption studies revealed HRV-C specific titres were markedly and significantly lower than the HRV-A and HRV-B specific titres (P<0.0001). A truncated construct of HRV-C VP1 showed greater specificity in detecting anti-HRV-C antibodies.

CONCLUSIONS

High titres of IgG1 antibody were bound by the VP1 capsid proteins of HRV-A, -B and -C, but for the majority of people, a large proportion of the antibody to HRV-C was cross-reactive, especially to HRV-A. The improved specificity found for the truncated HRV-C VP1 indicates species-specific and cross-reactive regions could be defined.

摘要

背景

人类鼻病毒(HRV)与上呼吸道和下呼吸道疾病有关,包括导致儿童和成人住院的严重感染。尽管 HRV 感染的临床意义现在已经得到充分证实,但尚未对针对 HRV 的免疫反应进行详细调查。本研究的目的是评估健康受试者中三种已知 HRV 种(HRV-A、-B 和 -C)的 IgG1 抗体反应。

方法

HRV-A、-B 和 -C 的两种基因型的病毒衣壳蛋白 1(VP1)的重组多肽作为谷胱甘肽 S-转移酶(GST)融合蛋白表达,并通过亲和和尺寸排阻层析进行纯化。通过圆二色性分析验证了与天然抗原具有相似二级结构的存在。使用来自 63 名健康成年人的血清通过免疫测定和免疫吸附来定量测定总 IgG1 和种特异性 IgG1。

结果

大多数成人血清与 HRV VP1 抗原反应,效价高。正如预期的那样,同一物种的 HRV 基因型之间发现了强烈的交叉反应。不同 HRV 种之间也存在高度的交叉反应,尤其是 HRV-A 和 HRV-C 之间。免疫吸收研究表明,HRV-C 特异性效价明显且显著低于 HRV-A 和 HRV-B 特异性效价(P<0.0001)。HRV-C VP1 的截断构建体显示出在检测抗 HRV-C 抗体方面具有更高的特异性。

结论

HRV-A、-B 和 -C 的 VP1 衣壳蛋白结合了高滴度的 IgG1 抗体,但对于大多数人来说,HRV-C 的抗体中有很大一部分是交叉反应的,尤其是与 HRV-A。对于截断的 HRV-C VP1 发现的更高特异性表明可以定义种特异性和交叉反应性区域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f97b/3737412/4edb96ee8996/pone.0070552.g001.jpg

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