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UNRAVELING THE COMPLEXITY OF CHIKUNGUNYA VIRUS INFECTION IMMUNOLOGICAL AND GENETIC INSIGHTS IN ACUTE AND CHRONIC PATIENTS
Fritsch, Hegger et al. | Date Issued: 2024
Author
Fritsch, Hegger
Giovanetti, Marta
Clemente, Luan Gaspar
Fernandes, Gabriel da Rocha
Fonseca, Vagner
Lima, Maricelia Maia de
Falcão, Melissa
Jesus, Neuza de
Cerqueira, Erenilde Marques de
Cunha, Rivaldo Venâncio da
Francisco, Marcos Vinicius Lima de Oliveira
Siqueira, Isadora Cristina de
Oliveira, Carla de
Xavier, Joilson
Ferreira, Jorge Gomes Goulart
Queiroz, Fábio Ribeiro
Smith, Elise
Tisoncik-Go, Jennifer
Voorhis, Wesley C Van
Rabinowitz, Peter M
Wasserheit, Judith N
Gale Jr, Michael
Filippis, Ana Maria Bispo de
Alcantara, Luiz Carlos Junior
Affilliation
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, Brasil / Université de Tours. Institut National de la Santé et de la Recherche Médicale. Tours, France.
Università Campus Bio-Medico di Roma. Department of Science and Technologies for Sustainable Development and One Health. Rome, Italy /Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil /Doenças Amplificadas pelo Clima e Epidemias. Belo Horizonte, MG, Brasil.
Universidade de São Paulo. Escola Superior de Agricultura Luiz de Queiroz. Departamento de Zootecnia, Piracicaba, SP, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Universidade Estadual da Bahia. Departamento de Ciências Exatas e da Terra. Salvador, BA, Brazil / Stellenbosch University. Centre for Epidemic Response and Innovation. School of Data Science and Computational Thinking. Stellenbosch, South Africa.
Universidade Estadual de Feira de Santana. Departamento de Saúde. Feira de Santana, BA, Brasil/Prefeitura de Feira de Santana. Secretaria Municipal de Saúde. Divisão de Vigilância Epidemiológica. Feira de Santana, BA, Brasil.
Prefeitura de Feira de Santana. Secretaria Municipal de Saúde. Divisão de Vigilância Epidemiológica. Feira de Santana, BA, Brasil.
Prefeitura de Feira de Santana. Secretaria Municipal de Saúde. Divisão de Vigilância Epidemiológica. Feira de Santana, BA, Brasil.
Universidade Estadual de Feira de Santana. Departamento de Saúde. Feira de Santana, BA, Brazil.
Fundação Oswaldo Cruz. nstituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Arbovírus e Vírus Hemorrágicos. Rio de Janeiro, RJ, Brasil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, Brasil.
Instituto Mário Penna. Núcleo de Ensino, Pesquisa e Inovação. Belo Horizonte, MG, Brasil.
Instituto Mário Penna. Núcleo de Ensino, Pesquisa e Inovação. Belo Horizonte, MG, Brasil.
University of Washington.Department of Immunology. Seattle, WA, USA.
University of Washington.Department of Immunology. Seattle, WA, USA.
University of Washington. Department of Medicine. Seattle. WA, USA.
University of Washington. Departments of Environmental and Occupational Health Sciences. Seattle, WA, USA
University of Washington. Department of Global Health.Seattle, WA, USA.
University of Washington. Department of Immunology. Seattle, WA, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Arbovírus e Vírus Hemorrágicos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil/Doenças Amplificadas pelo Clima e Epidemias. Belo Horizonte, MG, Brazil.
Abstract
Background: 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. Objectives/Methods: 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. Results: 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. Conclusion: 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.
Keywords
Chikungunya chronicity
Chikungunya virus
RNA-sequencing
acute infection
immune response
immunological characterization
 
Publisher
MDPI
Citation
FRITSCH, Hegger et al. Unraveling the Complexity of Chikungunya Virus Infection Immunological and Genetic Insights in Acute and Chronic Patients. Genes, v. 15, n. 11, 1365, 2024.
DOI
10.3390/genes15111365
ISSN
2073-4425