Pathophysiology of chikungunya virus infection associated with fatal outcomes.

alphavirus arbovirus central nervous system infection chikungunya death chikungunya virus hemodynamic disorders inflammation mosquito-borne virus pathophysiology

Journal

Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316

Informations de publication

Date de publication:
08 Mar 2024
Historique:
received: 16 08 2023
revised: 08 12 2023
accepted: 16 02 2024
medline: 14 3 2024
pubmed: 14 3 2024
entrez: 13 3 2024
Statut: aheadofprint

Résumé

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.

Identifiants

DOI: 10.1016/j.chom.2024.02.011 PMID: 38479396
pubmed: 38479396
pii: S1931-3128(24)00054-4
doi: 10.1016/j.chom.2024.02.011
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

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.

Auteurs

William M 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.

Marcilio J Fumagalli (MJ)

Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.

Shirlene T S 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.

Pierina L 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.

Deyse C M 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.

Cristian Hernandez (C)

Department of Neurobiology, University of Texas Medical Branch, Galveston, TX, USA.

Ronaldo 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.

Jeany Delafiori (J)

Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, São Paulo, Brazil.

Darlan S 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.

Victor C Carregari (VC)

Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.

Stefanie P Muraro (SP)

Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.

Gabriela F Souza (GF)

Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.

Leda M Simões Mello (LM)

Laboratório Central de Saúde Pública do Ceará, Fortaleza, Ceará, Brazil.

Ingra M 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.

Yamilka Díaz (Y)

Department of Research in Virology and Biotechnology, Gorgas Memorial Institute of Health Studies, Panama, Panama.

Rodrigo B 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.

Lucas N Trentin (LN)

Institute of Chemistry and Center for Computing in Engineering and Sciences, University of Campinas, Campinas, São Paulo, Brazil.

Clauber H S Costa (CHS)

Institute of Chemistry and Center for Computing in Engineering and Sciences, University of Campinas, Campinas, São Paulo, Brazil.

Ana Carolina B M Maximo (ACBM)

Laboratório Central de Saúde Pública do Ceará, Fortaleza, Ceará, Brazil.

Karene F Cavalcante (KF)

Laboratório Central de Saúde Pública do Ceará, Fortaleza, Ceará, Brazil.

Tayna S 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.

Vânia A F Viana (VAF)

Laboratório Central de Saúde Pública do Ceará, Fortaleza, Ceará, Brazil.

Maria Elisabeth L Melo (MEL)

Laboratório Central de Saúde Pública do Ceará, Fortaleza, Ceará, Brazil.

Clarissa P M Ferraz (CPM)

Laboratório Central de Saúde Pública do Ceará, Fortaleza, Ceará, Brazil.

Débora B Silva (DB)

Laboratório Central de Saúde Pública do Ceará, Fortaleza, Ceará, Brazil.

Larissa M F Duarte (LMF)

Laboratório Central de Saúde Pública do Ceará, Fortaleza, Ceará, Brazil.

Priscilla P Barbosa (PP)

Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.

Mariene R Amorim (MR)

Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.

Carla C Judice (CC)

Laboratory of Tropical Diseases, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.

Daniel A Toledo-Teixeira (DA)

Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.

Mariana S 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.

Patricia V 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.

Emerson L L 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.

Fabio T M Costa (FTM)

Laboratory of Tropical Diseases, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.

Thiago 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.

Ricardo 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.

Viviane S 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.

Luiz Tadeu M Figueiredo (LTM)

Virology Research Centre, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.

Rong Fang (R)

Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.

Brechla Moreno (B)

Department of Research in Virology and Biotechnology, Gorgas Memorial Institute of Health Studies, Panama, Panama.

Sandra 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.

Liana Perdigão Mello (LP)

Laboratório Central de Saúde Pública do Ceará, Fortaleza, Ceará, Brazil.

Munir S Skaf (MS)

Institute of Chemistry and Center for Computing in Engineering and Sciences, University of Campinas, Campinas, São Paulo, Brazil.

Rodrigo R Catharino (RR)

Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, São Paulo, Brazil.

Fabiana 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.

Daniel 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.

Jessica A 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.

Kenneth S 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.

Ester C 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.

Michael S Diamond (MS)

Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO, USA.

Eliseo Eugenin (E)

Department of Neurobiology, University of Texas Medical Branch, Galveston, TX, USA.

José Luiz Proença-Módena (JL)

Laboratory of Emerging Viruses, Department of Genetics, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, São Paulo, Brazil.

Nuno R 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.

Scott C 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.

Classifications MeSH