Pathophysiology of chikungunya virus infection associated with fatal outcomes
File(s)
Published version
Author(s)
de Souza, William M
Fumagalli, Marcilio J
de Lima, Shirlene TS
Parise, Pierina L
Carvalho, Deyse CM
Type
Journal Article
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.
Date Issued
2024-04-10
Date Acceptance
2024-02-16
Citation
Cell Host and Microbe, 2024, 32 (4), pp.606-622.e8
ISSN
1931-3128
Publisher
Cell Press
Start Page
606
End Page
622.e8
Journal / Book Title
Cell Host and Microbe
Volume
32
Issue
4
Copyright Statement
© 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/38479396
PII: S1931-3128(24)00054-4
Subjects
BLOOD-BRAIN-BARRIER
CD14(+)CD16(+) MONOCYTES
DISEASE
Life Sciences & Biomedicine
Microbiology
MODEL
OUTBREAK
Parasitology
PECAM-1
PERFORMANCE
POTENTIAL ROLE
Science & Technology
SYSTEM
TRANSMIGRATION
Virology
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2024-03-12