Journal article
Dengue Virus Infection Alters Inter-Endothelial Junctions and Promotes Endothelial-Mesenchymal-Transition-Like Changes in Human Microvascular Endothelial Cells
Viruses, Vol.15(7), 1437
06/26/2023
DOI: 10.3390/v15071437
PMCID: PMC10386726
PMID: 37515125
Abstract
Dengue virus (DENV) is a pathogenic arbovirus that causes human disease. The most severe stage of the disease (severe dengue) is characterized by vascular leakage, hypovolemic shock, and organ failure. Endothelial dysfunction underlies these phenomena, but the causal mechanisms of endothelial dysfunction are poorly characterized. This study investigated the role of c-ABL kinase in DENV-induced endothelial dysfunction. Silencing c-ABL with artificial miRNA or targeting its catalytic activity with imatinib revealed that c-ABL is required for the early steps of DENV infection. DENV-2 infection and conditioned media from DENV-infected cells increased endothelial expression of c-ABL and CRKII phosphorylation, promoted expression of mesenchymal markers, e.g., vimentin and N-cadherin, and decreased the levels of endothelial-specific proteins, e.g., VE-cadherin and ZO-1. These effects were reverted by silencing or inhibiting c-ABL. As part of the acquisition of a mesenchymal phenotype, DENV infection and treatment with conditioned media from DENV-infected cells increased endothelial cell motility in a c-ABL-dependent manner. In conclusion, DENV infection promotes a c-ABL-dependent endothelial phenotypic change that leads to the loss of intercellular junctions and acquisition of motility.
Details
- Title: Subtitle
- Dengue Virus Infection Alters Inter-Endothelial Junctions and Promotes Endothelial-Mesenchymal-Transition-Like Changes in Human Microvascular Endothelial Cells
- Creators
- Manuela Escudero-Florez - Universidad de AntioquiaDavid Torres-Hoyos - Universidad de AntioquiaYaneth Miranda-Brand - Univ Antioquia, Mol & Translat Med Grp, Medellin 050010, ColombiaRyan L Boudreau - University of Iowa, Iowa Neuroscience InstituteJuan Carlos Gallego-Gomez - Universidad de AntioquiaMiguel Vicente-Manzanares - Univ Salamanca, Ctr Invest Canc, Consejo Super Invest Cient CSIC, Mol Mech Program,Inst Biol Mol & Celular Canc, Salamanca 37007, Spain
- Resource Type
- Journal article
- Publication Details
- Viruses, Vol.15(7), 1437
- DOI
- 10.3390/v15071437
- PMID
- 37515125
- PMCID
- PMC10386726
- NLM abbreviation
- Viruses
- ISSN
- 1999-4915
- eISSN
- 1999-4915
- Publisher
- Mdpi
- Number of pages
- 21
- Grant note
- name: Colombian Ministerio de Ciencia, Tecnología e Innovación, award: 111584466951; DOI: 10.13039/501100003329, name: Spanish Ministry of Science and Innovation, award: PID2020-116232RB-I00; name: Programa de Apoyo a Planes Estratégicos de Investigación de Estructuras de Investigación de Excelencia of the Ministry of Education of the Castilla–León Government, award: CLC–2017–01
- Language
- English
- Date published
- 06/26/2023
- Academic Unit
- Iowa Neuroscience Institute; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984508750402771
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