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CC BY 4.0 · Arq Neuropsiquiatr 2023; 81(04): 357-368
DOI: 10.1055/s-0043-1768698
Original Article

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

Mimetismo molecular entre o vírus Zika e os distúrbios inflamatórios desmielinizantes do sistema nervoso central: o papel do epítopo NS5 do vírus Zika e dos autoantígenos PLP
Laise Carolina França 
1   Universidade Federal do Estado do Rio de Janeiro, Programa de Pós-Graduação em Neurologia, Laboratório de Neurociências Translacional, Rio de Janeiro RJ, Brazil.
,
Fabrícia Lima Fontes-Dantas 
1   Universidade Federal do Estado do Rio de Janeiro, Programa de Pós-Graduação em Neurologia, Laboratório de Neurociências Translacional, Rio de Janeiro RJ, Brazil.
2   Universidade do Estado do Rio de Janeiro, Departamento de Farmacologia e Psicobiologia, Rio de Janeiro RJ, Brazil.
,
Diogo Gomes Garcia 
1   Universidade Federal do Estado do Rio de Janeiro, Programa de Pós-Graduação em Neurologia, Laboratório de Neurociências Translacional, Rio de Janeiro RJ, Brazil.
,
Amanda Dutra de Araújo 
1   Universidade Federal do Estado do Rio de Janeiro, Programa de Pós-Graduação em Neurologia, Laboratório de Neurociências Translacional, Rio de Janeiro RJ, Brazil.
,
João Paulo da Costa Gonçalves 
1   Universidade Federal do Estado do Rio de Janeiro, Programa de Pós-Graduação em Neurologia, Laboratório de Neurociências Translacional, Rio de Janeiro RJ, Brazil.
,
Cláudia Cecília da Silva Rêgo 
1   Universidade Federal do Estado do Rio de Janeiro, Programa de Pós-Graduação em Neurologia, Laboratório de Neurociências Translacional, Rio de Janeiro RJ, Brazil.
,
Elielson Veloso da Silva 
1   Universidade Federal do Estado do Rio de Janeiro, Programa de Pós-Graduação em Neurologia, Laboratório de Neurociências Translacional, Rio de Janeiro RJ, Brazil.
,
Osvaldo José Moreira do Nascimento 
3   Universidade Federal Fluminense, Hospital Universitário Antônio Pedro, Departamento de Neurologia, Niterói RJ, Brazil.
,
Fernanda Cristina Rueda Lopes 
4   Universidade Federal Fluminense, Hospital Universitário Antônio Pedro, Departamento de Radiologia, Niterói RJ, Brazil.
,
Alice Laschuk Herlinger 
4   Universidade Federal Fluminense, Hospital Universitário Antônio Pedro, Departamento de Radiologia, Niterói RJ, Brazil.
,
Renato Santana de Aguiar 
4   Universidade Federal Fluminense, Hospital Universitário Antônio Pedro, Departamento de Radiologia, Niterói RJ, Brazil.
,
Orlando da Costa Ferreira Junior 
5   Universidade Federal do Rio de Janeiro, Instituto de Biologia, Departamento de Genética, Rio de Janeiro RJ, Brazil.
,
Fernando Faria Andrade Figueira 
6   Hospital São Francisco na Providência de Deus, Departamento de Neurologia, Rio de Janeiro RJ, Brazil.
,
Jorge Paes Barreto Marcondes de Souza 
1   Universidade Federal do Estado do Rio de Janeiro, Programa de Pós-Graduação em Neurologia, Laboratório de Neurociências Translacional, Rio de Janeiro RJ, Brazil.
7   Universidade Federal do Rio de Janeiro, Hospital Universitário Clementino Fraga Filho, Departamento de Neurocirurgia, Rio de Janeiro RJ, Brazil.
,
Joelma Freire De Mesquita 
8   Universidade Federal do Estado do Rio de Janeiro, Departamento de Genética e Biologia Molecular, Grupo de Bioinformática e Biologia Computacional, Rio de Janeiro RJ, Brazil.
,
Soniza Vieira Alves-Leon 
1   Universidade Federal do Estado do Rio de Janeiro, Programa de Pós-Graduação em Neurologia, Laboratório de Neurociências Translacional, Rio de Janeiro RJ, Brazil.
9   Universidade Federal do Rio de Janeiro, Hospital Universitário Clementino Fraga Filho, Centro de Referência e Pesquisa em Esclerose Múltipla e Outras Doenças Desmielinizantes Inflamatórias Idiopáticas do SNC, Rio de Janeiro RJ, Brazil.
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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.

Resumo

Antecedentes Evidências indicam uma forte ligação entre o vírus Zika (ZikV) e complicações neurológicas. Mielite aguda, neurite óptica, polineuropatia e encefalomielite que mimetizam distúrbios inflamatórios de desmielinização idiopáticos (DDII) após infecção por ZikV têm sido relatadas no Brasil.

Obejtivo O presente estudo tem como objetivo investigar a possível ocorrência de mimetismo molecular entre antígenos do ZikV e autoantígenos da Esclerose Múltipla (EM), a DDII mais frequente do sistema nervoso central (SNC).

Métodos Foi realizado um estudo de coorte retrospectivo com 305 pacientes internados por suspeita de infecção por arbovírus no Rio de Janeiro, todos os indivíduos foram submetidos a exame neurológico e coleta de amostra biológica para diagnóstico sorológico e molecular. Ferramentas de bioinformática foram usadas para analisar os peptídeos compartilhados entre antígenos do ZikV e autoantígenos da EM.

Resultados Dos 305 pacientes, vinte e seis foram positivos para ZikV e 4 apresentaram padrão IDD encontrado em casos de EM. As comparações de homologia de sequência por abordagem de bioinformática entre a proteína NS5 ZikV e PLP EM revelaram uma homologia de 5/6 aminoácidos consecutivos (CSSVPV/CSAVPV) com 83% de identidade, deduzindo um mimetismo molecular. A análise das estruturas 3D revelou uma conformação semelhante com apresentação em alfa-hélice.

Conclusões O mimetismo molecular entre o antígeno NS5 do vírus Zika e o autoantígeno PLP da EM surge como um possível mecanismo para o espectro IDD em indivíduos geneticamente suscetíveis.

Keyword

Zika Virus - Demyelinating Diseases - Molecular Mimicry - Viral Nonstructural Proteins - Multiple Sclerosis

Palavras-chave

Zika Virus - Doenças Desmielinizantes - Mimetismo Molecular - Proteínas não Estruturais Virais - Esclerose Múltipla

Authors' Contributions

SVAL, FLFD: conceived and designed the experiments; SVAL, FLFD, LCF, DGG, ADA, JPCG, CCSR, EVS, OJMN, FCRL, FFAF, JPBMS: subject recruitment and collection of the samples; ALH, RSA, OCFJ: serology and molecular diagnostic; FLFD, LCF, JFM: performing bioinformatics analyzes; LCF, FLFD, SVAL: analyzed the data and drafted the manuscript; LCF, FLFD: contributed equally to this work. All authors read and approved the final version.


Support

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Brazilian National Council for Scientific and Technological Development (CNPq Number 440779/2016-2), Coordination for the Improvement of Higher Education Personnel (CAPES Number 88887.130752/2016-00), Department of Science and Technology (DECIT No. 14/2016), Rede Nacional de Especialistas em ZIKA e Doenças Correlatas (RENEZIKA) and Foundation for Rio de Janeiro State Research (FAPERJ).




Publikationsverlauf

Eingereicht: 09. Mai 2022

Angenommen: 16. Dezember 2022

Artikel online veröffentlicht:
09. Mai 2023

© 2023. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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