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寨卡病毒E糖蛋白环区与格林-巴利综合征相关蛋白:疫苗研发中需考虑的一种可能的分子模拟现象

Zika E Glycan Loop Region and Guillain-Barré Syndrome-Related Proteins: A Possible Molecular Mimicry to Be Taken in Account for Vaccine Development.

作者信息

Lebeau Grégorie, Frumence Etienne, Turpin Jonathan, Begue Floran, Hoarau Jean-Jacques, Gadea Gilles, Krejbich-Trotot Pascale, Desprès Philippe, Viranaicken Wildriss

机构信息

Processus Infectieux en Milieu Insulaire et Tropical (PIMIT), Université de La Réunion 1, La Réunion, 97490 Sainte-Clotilde, France.

Université de La Réunion, INSERM, UMR 1188 Diabète athérothombose Réunion Océan Indien (DéTROI), 97490 Saint-Clotilde, France.

出版信息

Vaccines (Basel). 2021 Mar 19;9(3):283. doi: 10.3390/vaccines9030283.

Abstract

The neurological complications of infection by the mosquito-borne Zika virus (ZIKV) include Guillain-Barré syndrome (GBS), an acute inflammatory demyelinating polyneuritis. GBS was first associated with recent ZIKV epidemics caused by the emergence of the ZIKV Asian lineage in South Pacific. Here, we hypothesize that ZIKV-associated GBS relates to a molecular mimicry between viral envelope E (E) protein and neural proteins involved in GBS. The analysis of the ZIKV epidemic strains showed that the glycan loop (GL) region of the E protein includes an IVNDT motif which is conserved in voltage-dependent L-type calcium channel subunit alpha-1C (Ca1.2) and Heat Shock 70 kDa protein 12A (HSP70 12A). Both VSCC-alpha 1C and HSP70 12A belong to protein families which have been associated with neurological autoimmune diseases in central nervous system. The purpose of our analysis is to point out that IVNDT motif of ZIKV E-GL region should be taken in consideration for the development of safe and effective anti-Zika vaccines by precluding the possibility of adverse neurologic events including autoimmune diseases such as GBS through a potent mimicry with Heat Shock 70 kDa protein 12A (HSP70 12A).

摘要

由蚊媒传播的寨卡病毒(ZIKV)感染引起的神经并发症包括吉兰-巴雷综合征(GBS),这是一种急性炎症性脱髓鞘性多发性神经炎。GBS最初与南太平洋出现的ZIKV亚洲谱系引发的近期ZIKV疫情有关。在此,我们假设ZIKV相关的GBS与病毒包膜E(E)蛋白和参与GBS的神经蛋白之间的分子模拟有关。对ZIKV流行毒株的分析表明,E蛋白的糖基化环(GL)区域包含一个IVNDT基序,该基序在电压依赖性L型钙通道亚基α-1C(Ca1.2)和热休克70 kDa蛋白12A(HSP70 12A)中保守。VSCC-α 1C和HSP70 12A都属于与中枢神经系统神经自身免疫性疾病相关的蛋白家族。我们分析的目的是指出,在开发安全有效的抗寨卡疫苗时,应考虑ZIKV E-GL区域的IVNDT基序,通过与热休克70 kDa蛋白12A(HSP70 12A)的有效模拟,排除包括GBS等自身免疫性疾病在内的不良神经事件发生的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af3d/8003386/fd09f92b5cd1/vaccines-09-00283-g001.jpg

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