학술논문

Pathophysiology of chikungunya virus infection associated with fatal outcomes.
Document Type
Academic Journal
Author
de Souza WM; Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, College of Medicine, Lexington, KY, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA; Global Virus Network, Baltimore, MD, USA. Electronic address: wmdesouza@uky.edu.; Fumagalli MJ; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.; de Lima STS; Laboratório Central de Saúde Pública do Ceará, Fortaleza, Ceará, Brazil; Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.; Parise PL; Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.; Carvalho DCM; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Laboratory of Immunobiotechnology, Biotechnology Center, Federal University of Paraíba, João Pessoa, Paraíba, Brazil.; Hernandez C; Department of Neurobiology, University of Texas Medical Branch, Galveston, TX, USA.; de Jesus R; Coordenação Geral dos Laboratórios de Saúde Pública, Secretaria de Vigilância em Saúde, Ministério da Saúde, Brasília, Brazil; Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.; Delafiori J; Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, São Paulo, Brazil.; Candido DS; MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, UK; Department of Zoology, University of Oxford, Oxford, UK; Instituto de Medicina Tropical, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.; Carregari VC; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.; Muraro SP; Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.; Souza GF; Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.; Simões Mello LM; Laboratório Central de Saúde Pública do Ceará, Fortaleza, Ceará, Brazil.; Claro IM; MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, UK; Instituto de Medicina Tropical, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.; Díaz Y; Department of Research in Virology and Biotechnology, Gorgas Memorial Institute of Health Studies, Panama, Panama.; Kato RB; Coordenação Geral dos Laboratórios de Saúde Pública, Secretaria de Vigilância em Saúde, Ministério da Saúde, Brasília, Brazil; Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.; Trentin LN; Institute of Chemistry and Center for Computing in Engineering and Sciences, University of Campinas, Campinas, São Paulo, Brazil.; Costa CHS; Institute of Chemistry and Center for Computing in Engineering and Sciences, University of Campinas, Campinas, São Paulo, Brazil.; Maximo ACBM; Laboratório Central de Saúde Pública do Ceará, Fortaleza, Ceará, Brazil.; Cavalcante KF; Laboratório Central de Saúde Pública do Ceará, Fortaleza, Ceará, Brazil.; Fiuza TS; Laboratório Central de Saúde Pública do Ceará, Fortaleza, Ceará, Brazil; Programa de Pós Graduação em Bioinformática, Instituto Metrópole Digital, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.; Viana VAF; Laboratório Central de Saúde Pública do Ceará, Fortaleza, Ceará, Brazil.; Melo MEL; Laboratório Central de Saúde Pública do Ceará, Fortaleza, Ceará, Brazil.; Ferraz CPM; Laboratório Central de Saúde Pública do Ceará, Fortaleza, Ceará, Brazil.; Silva DB; Laboratório Central de Saúde Pública do Ceará, Fortaleza, Ceará, Brazil.; Duarte LMF; Laboratório Central de Saúde Pública do Ceará, Fortaleza, Ceará, Brazil.; Barbosa PP; Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.; Amorim MR; Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.; Judice CC; Laboratory of Tropical Diseases, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.; Toledo-Teixeira DA; Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.; Ramundo MS; Instituto de Medicina Tropical, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.; Aguilar PV; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA; Center for Tropical Diseases, Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, TX, USA.; Araújo ELL; Coordenação Geral de Atenção às Doenças Transmissíveis na Atenção Primária, Departamento de Gestão ao cuidado Integral, Secretaria de Atenção Primária à Saúde, Ministério da Saúde, Brasília, Brazil.; Costa FTM; Laboratory of Tropical Diseases, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.; Cerqueira-Silva T; Universidade Federal da Bahia, Faculdade de Medicina, Salvador, Bahia, Brazil; Fundação Oswaldo Cruz, Instituto Gonçalo Muniz, Laboratório de Medicina e Saúde Pública de Precisão, Salvador, Bahia, Brazil.; Khouri R; Universidade Federal da Bahia, Faculdade de Medicina, Salvador, Bahia, Brazil; Fundação Oswaldo Cruz, Instituto Gonçalo Muniz, Laboratório de Medicina e Saúde Pública de Precisão, Salvador, Bahia, Brazil.; Boaventura VS; Universidade Federal da Bahia, Faculdade de Medicina, Salvador, Bahia, Brazil; Fundação Oswaldo Cruz, Instituto Gonçalo Muniz, Laboratório de Medicina e Saúde Pública de Precisão, Salvador, Bahia, Brazil; Hospital Santa Izabel, Santa Casa de Misericórdia da Bahia, Serviço de Otorrinolaringologia, Salvador, Bahia, Brazil.; Figueiredo LTM; Virology Research Centre, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.; Fang R; Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.; Moreno B; Department of Research in Virology and Biotechnology, Gorgas Memorial Institute of Health Studies, Panama, Panama.; López-Vergès S; Department of Research in Virology and Biotechnology, Gorgas Memorial Institute of Health Studies, Panama, Panama; Sistema Nacional de Investigación from SENACYT, Panama, Panama.; Mello LP; Laboratório Central de Saúde Pública do Ceará, Fortaleza, Ceará, Brazil.; Skaf MS; Institute of Chemistry and Center for Computing in Engineering and Sciences, University of Campinas, Campinas, São Paulo, Brazil.; Catharino RR; Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, São Paulo, Brazil.; Granja F; Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil; Biodiversity Research Centre, Federal University of Roraima, Boa Vista, Roraima, Brazil.; Martins-de-Souza D; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil; D'Or Institute for Research and Education, São Paulo, São Paulo, Brazil; Experimental Medicine Research Cluster, University of Campinas, Campinas, São Paulo, Brazil.; Plante JA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA.; Plante KS; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA.; Sabino EC; Instituto de Medicina Tropical, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.; Diamond MS; Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO, USA.; Eugenin E; Department of Neurobiology, University of Texas Medical Branch, Galveston, TX, USA.; Proença-Módena JL; Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.; Faria NR; MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, UK; Department of Zoology, University of Oxford, Oxford, UK; Instituto de Medicina Tropical, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.; Weaver SC; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA; Global Virus Network, Baltimore, MD, USA; Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
Source
Publisher: Cell Press Country of Publication: United States NLM ID: 101302316 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1934-6069 (Electronic) Linking ISSN: 19313128 NLM ISO Abbreviation: Cell Host Microbe Subsets: MEDLINE
Subject
Language
English
Abstract
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes acute, subacute, and chronic human arthritogenic diseases and, in rare instances, can lead to neurological complications and death. Here, we combined epidemiological, virological, histopathological, cytokine, molecular dynamics, metabolomic, proteomic, and genomic analyses to investigate viral and host factors that contribute to chikungunya-associated (CHIK) death. Our results indicate that CHIK deaths are associated with multi-organ infection, central nervous system damage, and elevated serum levels of pro-inflammatory cytokines and chemokines compared with survivors. The histopathologic, metabolite, and proteomic signatures of CHIK deaths reveal hemodynamic disorders and dysregulated immune responses. The CHIKV East-Central-South-African lineage infecting our study population causes both fatal and survival cases. Additionally, CHIKV infection impairs the integrity of the blood-brain barrier, as evidenced by an increase in permeability and altered tight junction protein expression. Overall, our findings improve the understanding of CHIK pathophysiology and the causes of fatal infections.
Competing Interests: Declaration of interests M.S.D. is a consultant or advisor for Inbios, Ocugen, Vir Biotechnology, Topspin Therapeutics, Moderna, Merck, and Immunome. The Diamond laboratory has received funding support from Emergent BioSolutions, Moderna, and Vir Biotechnology.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)