1. Pathophysiology of chikungunya virus infection associated with fatal outcomes.
- Author
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de Souza WM, Fumagalli MJ, de Lima STS, Parise PL, Carvalho DCM, Hernandez C, de Jesus R, Delafiori J, Candido DS, Carregari VC, Muraro SP, Souza GF, Simões Mello LM, Claro IM, Díaz Y, Kato RB, Trentin LN, Costa CHS, Maximo ACBM, Cavalcante KF, Fiuza TS, Viana VAF, Melo MEL, Ferraz CPM, Silva DB, Duarte LMF, Barbosa PP, Amorim MR, Judice CC, Toledo-Teixeira DA, Ramundo MS, Aguilar PV, Araújo ELL, Costa FTM, Cerqueira-Silva T, Khouri R, Boaventura VS, Figueiredo LTM, Fang R, Moreno B, López-Vergès S, Mello LP, Skaf MS, Catharino RR, Granja F, Martins-de-Souza D, Plante JA, Plante KS, Sabino EC, Diamond MS, Eugenin E, Proença-Módena JL, Faria NR, and Weaver SC
- Subjects
- Animals, Humans, Proteomics, Cytokines metabolism, Chikungunya Fever complications, Chikungunya virus genetics
- 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.)
- Published
- 2024
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