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

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).

Publication History

Received: 09 May 2022

Accepted: 16 December 2022

Article published online:
09 May 2023

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