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Tytuł pozycji:

H5N1 infection impairs the alveolar epithelial barrier through intercellular junction proteins via Itch-mediated proteasomal degradation.

Tytuł:
H5N1 infection impairs the alveolar epithelial barrier through intercellular junction proteins via Itch-mediated proteasomal degradation.
Autorzy:
Ruan T; College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, China.
Sun Y; College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, China.
Zhang J; College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, China.
Sun J; College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, China.; Institute of Comparative Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, China.
Liu W; College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, China.
Prinz RA; Department of Surgery, NorthShore University Health System, Evanston, IL, 60201, USA.
Peng D; Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province, 225009, China.; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, 225009, Jiangsu Province, China.
Liu X; Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province, 225009, China.; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, 225009, Jiangsu Province, China.
Xu X; College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, China. .; Institute of Comparative Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu Province, China. .; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, 225009, Jiangsu Province, China. .
Źródło:
Communications biology [Commun Biol] 2022 Mar 01; Vol. 5 (1), pp. 186. Date of Electronic Publication: 2022 Mar 01.
Typ publikacji:
Journal Article; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Original Publication: London, United Kingdom : Nature Publishing Group UK, [2018]-
MeSH Terms:
Alveolar Epithelial Cells*/metabolism
Alveolar Epithelial Cells*/virology
Influenza A Virus, H5N1 Subtype*
Ubiquitin-Protein Ligases*/genetics
Ubiquitin-Protein Ligases*/metabolism
Animals ; Intercellular Junctions/genetics ; Intercellular Junctions/metabolism ; Intercellular Junctions/virology ; Lung/pathology ; Lung/virology ; Mice
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Substance Nomenclature:
EC 2.3.2.26 (Itch protein, mouse)
EC 2.3.2.27 (Ubiquitin-Protein Ligases)
Entry Date(s):
Date Created: 20220302 Date Completed: 20220404 Latest Revision: 20221025
Update Code:
20240104
PubMed Central ID:
PMC8888635
DOI:
10.1038/s42003-022-03131-3
PMID:
35233032
Czasopismo naukowe
The H5N1 subtype of the avian influenza virus causes sporadic but fatal infections in humans. H5N1 virus infection leads to the disruption of the alveolar epithelial barrier, a pathologic change that often progresses into acute respiratory distress syndrome (ARDS) and pneumonia. The mechanisms underlying this remain poorly understood. Here we report that H5N1 viruses downregulate the expression of intercellular junction proteins (E-cadherin, occludin, claudin-1, and ZO-1) in several cell lines and the lungs of H5N1 virus-infected mice. H5N1 virus infection activates TGF-β-activated kinase 1 (TAK1), which then activates p38 and ERK to induce E3 ubiquitin ligase Itch expression and to promote occludin ubiquitination and degradation. Inhibition of the TAK1-Itch pathway restores the intercellular junction structure and function in vitro and in the lungs of H5N1 virus-infected mice. Our study suggests that H5N1 virus infection impairs the alveolar epithelial barrier by downregulating the expression of intercellular junction proteins at the posttranslational level.
(© 2022. The Author(s).)
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