Unraveling the Complexity of Chikungunya Virus Infection Immunological and Genetic Insights in Acute and Chronic Patients

<b>Background</b>: The chikungunya virus (CHIKV), transmitted by infected Aedes mosquitoes, has caused a significant number of infections worldwide. In Brazil, the emergence of the CHIKV-ECSA genotype in 2014 posed a major public health challenge due to its association with more severe symptoms. <b>Objectives/Methods</b>: This study aimed to shed new light on the host immune response by examining the whole-blood transcriptomic profile of both CHIKV-acute and chronically infected individuals from Feira de Santana, Bahia, Brazil, a region heavily affected by CHIKV, Dengue, and Zika virus epidemics. <b>Results</b>: Our data reveal complex symptomatology characterized by arthralgia and post-chikungunya neuropathy in individuals with chronic sequelae, particularly affecting women living in socially vulnerable situations. Analysis of gene modules suggests heightened metabolic processes, represented by an increase in NADH, COX5A, COA3, CYC1, and cap methylation in patients with acute disease. In contrast, individuals with chronic manifestations exhibit a distinct pattern of histone methylation, probably mediated by NCOA3 in the coactivation of different nuclear receptors, KMT2 genes, KDM3B and TET2, and with alterations in the immunological response, majorly led by IL-17RA, IL-6R, and STAT3 Th17 genes. <b>Conclusion</b>: Our results emphasize the complexity of CHIKV disease progression, demonstrating the heterogeneous gene expression and symptomatologic scenario across both acute and chronic phases. Moreover, the identification of specific gene modules associated with viral pathogenesis provides critical insights into the molecular mechanisms underlying these distinct clinical manifestations.

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Publication Details

Journal
Genes
Published
2024-10-24
DOI
https://doi.org/10.3390/genes15111365
Citations
2
Primary Topic
Mosquito-borne diseases and control
Type
article
Field-Weighted Citation Impact
1.09

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article

Unraveling the Complexity of Chikungunya Virus Infection Immunological and Genetic Insights in Acute and Chronic Patients

Judith N. Wasserheit, Rivaldo Venâncio da Cunha, Wesley C. Van Voorhis, Melissa Falcão et al.
2 citations
Genes
Mosquito-borne diseases and control
1.09
article

Unraveling the Complexity of Chikungunya Virus Infection Immunological and Genetic Insights in Acute and Chronic Patients

Judith N. Wasserheit, Rivaldo Venâncio da Cunha, Wesley C. Van Voorhis, Melissa Falcão, Luan Gaspar Clemente, Maricélia Maia de Lima, Peter Rabinowitz, Marcos Vinícius Lima de Oliveira Francisco, Jorge G. Ferreira, Joilson Xavier, Michael Gale, Fábio Ribeiro Queiroz, Luíz Carlos Júnior Alcântara, Isadora Cristina de Siqueira, Marta Giovanetti, Vagner Fonseca, Hegger Fritsch, Gabriel da Rocha Fernandes, Jennifer Tisoncik-Go, Erenilde Marques de Cerqueira, Ana María Bispo de Filippis, Carla Santos de Oliveira, Elise Smith, Nidia De Jesus
article en
2 citations

Abstract

<b>Background</b>: The chikungunya virus (CHIKV), transmitted by infected Aedes mosquitoes, has caused a significant number of infections worldwide. In Brazil, the emergence of the CHIKV-ECSA genotype in 2014 posed a major public health challenge due to its association with more severe symptoms. <b>Objectives/Methods</b>: This study aimed to shed new light on the host immune response by examining the whole-blood transcriptomic profile of both CHIKV-acute and chronically infected individuals from Feira de Santana, Bahia, Brazil, a region heavily affected by CHIKV, Dengue, and Zika virus epidemics. <b>Results</b>: Our data reveal complex symptomatology characterized by arthralgia and post-chikungunya neuropathy in individuals with chronic sequelae, particularly affecting women living in socially vulnerable situations. Analysis of gene modules suggests heightened metabolic processes, represented by an increase in NADH, COX5A, COA3, CYC1, and cap methylation in patients with acute disease. In contrast, individuals with chronic manifestations exhibit a distinct pattern of histone methylation, probably mediated by NCOA3 in the coactivation of different nuclear receptors, KMT2 genes, KDM3B and TET2, and with alterations in the immunological response, majorly led by IL-17RA, IL-6R, and STAT3 Th17 genes. <b>Conclusion</b>: Our results emphasize the complexity of CHIKV disease progression, demonstrating the heterogeneous gene expression and symptomatologic scenario across both acute and chronic phases. Moreover, the identification of specific gene modules associated with viral pathogenesis provides critical insights into the molecular mechanisms underlying these distinct clinical manifestations.

GenesVol. 15(11)
Université de Tours (FR), Universidade Federal de Minas Gerais (BR), Inserm (FR), Università Campus Bio-Medico (IT), Universidade de São Paulo (BR), University of Washington (US), Universidade Estadual de Feira de Santana (BR), Stellenbosch University (ZA), Instituto de Ensino e Pesquisa Santa Casa (BR), Secretaria de Agricultura e Abastecimento (BR), Secretaria Municipal de Saúde (BR), Fundação Oswaldo Cruz (BR)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Ministério da Saúde, Fundação Oswaldo Cruz, National Institutes of Health
Good health and well-being
Openalex Percentile: Top 20%
Mosquito-borne diseases and control
1.09
DOIOpen Access PDFOpenAlex
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