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寨卡病毒与中枢神经系统炎症性脱髓鞘疾病的分子模拟:NS5 寨卡病毒表位和 PLP 自身抗原的作用。

Molecular mimicry between Zika virus and central nervous system inflammatory demyelinating disorders: the role of NS5 Zika virus epitope and PLP autoantigens.

机构信息

Universidade Federal do Estado do Rio de Janeiro, Programa de Pós-Graduação em Neurologia, Laboratório de Neurociências Translacional, Rio de Janeiro RJ, Brazil.

Universidade do Estado do Rio de Janeiro, Departamento de Farmacologia e Psicobiologia, Rio de Janeiro RJ, Brazil.

出版信息

Arq Neuropsiquiatr. 2023 Apr;81(4):357-368. doi: 10.1055/s-0043-1768698. Epub 2023 May 9.

DOI:10.1055/s-0043-1768698
PMID:37160141
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10169219/
Abstract

BACKGROUND

Evidence indicates a strong link between Zika virus (ZikV) and neurological complications. Acute myelitis, optic neuritis, polyneuropathy, and encephalomyelitis that mimic inflammatory idiopathic demyelination disorders (IIDD) after ZikV infection have been reported in Brazil.

OBJECTIVE

The present study aims to investigate the possible occurrence of molecular mimicry between ZikV antigens and Multiple Sclerosis (MS) autoantigens, the most frequent IIDD of the central nervous system (CNS).

METHODS

A retrospective cohort study with 305 patients admitted due to suspected arbovirus infection in Rio de Janeiro was performed, all subjects were submitted to neurological examination, and a biological sample was collected for serologic and molecular diagnostic. Bioinformatics tools were used to analyze the peptides shared between ZikV antigens and MS autoantigens.

RESULTS

Of 305 patients, twenty-six were positive for ZikV and 4 presented IDD patterns found in MS cases. Sequence homology comparisons by bioinformatics approach between NS5 ZikV and PLP MS protein revealed a homology of 5/6 consecutive amino acids (CSSVPV/CSAVPV) with 83% identity, deducing a molecular mimicry. Analysis of the 3D structures revealed a similar conformation with alpha helix presentation.

CONCLUSIONS

Molecular mimicry between NS5 Zika virus antigen and PLP MS autoantigens emerge as a possible mechanism for IDD spectrum in genetically susceptible individuals.

摘要

背景

有证据表明寨卡病毒(ZikV)与神经系统并发症之间存在密切关联。巴西曾报告过寨卡病毒感染后类似于炎症性特发性脱髓鞘疾病(IIDD)的急性脊髓炎、视神经炎、多发性神经病和脑脊髓炎。

目的

本研究旨在探讨寨卡病毒抗原与多发性硬化症(MS)自身抗原之间是否存在分子模拟的可能性,MS 是中枢神经系统(CNS)最常见的 IIDD。

方法

对在里约热内卢因疑似虫媒病毒感染而住院的 305 例患者进行了回顾性队列研究,所有患者均接受了神经系统检查,并采集了生物样本进行血清学和分子诊断。生物信息学工具用于分析寨卡病毒抗原和 MS 自身抗原之间共享的肽段。

结果

在 305 例患者中,26 例 ZikV 阳性,4 例患者出现 MS 病例中发现的 IDD 模式。通过生物信息学方法对 NS5 寨卡病毒和 PLP MS 蛋白进行序列同源性比较,发现 5/6 个连续氨基酸(CSSVPV/CSAVPV)具有 83%的同源性,推断存在分子模拟。3D 结构分析显示具有相似的α螺旋构象。

结论

NS5 寨卡病毒抗原与 PLP MS 自身抗原之间的分子模拟可能是遗传易感个体发生 IDD 谱的一种机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45c7/10169219/899c3ce841a9/10-1055-s-0043-1768698-i220092-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45c7/10169219/a88af1142281/10-1055-s-0043-1768698-i220092-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45c7/10169219/c289574db3a5/10-1055-s-0043-1768698-i220092-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45c7/10169219/32578d301183/10-1055-s-0043-1768698-i220092-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45c7/10169219/cbe2507e2108/10-1055-s-0043-1768698-i220092-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45c7/10169219/899c3ce841a9/10-1055-s-0043-1768698-i220092-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45c7/10169219/a88af1142281/10-1055-s-0043-1768698-i220092-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45c7/10169219/c289574db3a5/10-1055-s-0043-1768698-i220092-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45c7/10169219/32578d301183/10-1055-s-0043-1768698-i220092-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45c7/10169219/cbe2507e2108/10-1055-s-0043-1768698-i220092-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45c7/10169219/899c3ce841a9/10-1055-s-0043-1768698-i220092-5.jpg

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