Altered Moesin and Actin Cytoskeleton Protein Rearrangements Affect Transendothelial Permeability in Human Endothelial Cells upon Dengue Virus Infection and TNF-α Treatment
| Autor: | Onrapak Reamtong, Sa-Nga Pattanakitsakul, Nantapon Rawarak, Thanaporn Mahutchariyakul, Aroonroong Suttitheptumrong, Kobporn Boonnak |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Proteomics
Stress fiber Moesin Vascular permeability macromolecular substances Dengue virus medicine.disease_cause Microbiology Article Permeability Capillary Permeability Dengue Virology medicine Humans transendothelial permeability cytoskeleton protein Cytoskeleton Actin biology Chemistry Tumor Necrosis Factor-alpha Microfilament Proteins Endothelial Cells Vinculin Dengue Virus Actin cytoskeleton dengue virus infection QR1-502 Actins Cell biology Actin Cytoskeleton Infectious Diseases biology.protein TNF-alpha |
| Zdroj: | Viruses Viruses, Vol 13, Iss 2042, p 2042 (2021) Volume 13 Issue 10 |
| ISSN: | 1999-4915 |
| Popis: | It has been hypothesized that the host, viral factors, and secreted cytokines (especially TNF-α) play roles in the pathogenesis of secondary dengue infections. Mass spectrometry-based proteomic screening of cytoskeleton fractions isolated from human endothelial (EA.hy926) cells upon dengue virus (DENV) infection and TNF-α treatment identified 450 differentially altered proteins. Among them, decreased levels of moesin, actin stress fiber rearrangements, and dot-like formations of vinculin were observed with western blot analyses and/or immunofluorescence staining (IFA). In vitro vascular permeability assays using EA.hy926 cells, seeded on collagen-coated transwell inserts, showed low levels of transendothelial electrical resistance in treated cells. The synergistic effects of DENV infection and TNF-α treatment caused cellular permeability changes in EA.hy926 cells, which coincided with decreasing moesin levels and the production of abnormal organizations of actin stress fibers and vinculin. Functional studies demonstrated moesin overexpression restored transendothelial permeability in DENV/TNF-α-treated EA.hy926 cells. The present study improves the understanding of the disruption mechanisms of cytoskeleton proteins in enhancing vascular permeability during DENV infection and TNF-α treatment. The study also suggests that these disruption mechanisms are major factors contributing to vascular leakage in severe dengue patients. |
| Databáze: | OpenAIRE |
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