Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Ion Channel Activity Promotes Virus Fitness and Pathogenesis
Visualitza/
Impacte
Scholar |
Altres documents de l'autoria: Nieto Torres, José L.; De Diego, Marta L.; Verdiá Báguena, Carmen; Jiménez Guardeño, José M.; Regla Nava, José A.; Fernández Delgado, Raúl; Castaño Rodríguez, Carlos; Alcaraz, Antonio; Torres, Jaume; Aguilella, Vicente; Enjuanes, Luis
Metadades
Mostra el registre complet de l'elementcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/2507
comunitat-uji-handle3:10234/6973
comunitat-uji-handle4:
INVESTIGACIONMetadades
Títol
Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Ion Channel Activity Promotes Virus Fitness and PathogenesisAutoria
Data de publicació
2014Editor
Public Library of ScienceISSN
1553-7366; 1553-7374Cita bibliogràfica
Nieto-Torres JL, DeDiego ML, Verdiá-Báguena C, Jimenez-Guardeño JM, Regla-Nava JA, Fernandez-Delgado R, et al. (2014) Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Ion Channel Activity Promotes Virus Fitness and Pathogenesis. PLoS Pathog 10(5): e1004077. doi:10.1371/journal.ppat.1004077Tipus de document
info:eu-repo/semantics/articleVersió de l'editorial
http://www.plospathogens.org/article/fetchObject.action?uri=info:doi/10.1371/jou ...Versió
info:eu-repo/semantics/publishedVersionResum
Deletion of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) envelope (E) gene attenuates the virus. E gene
encodes a small multifunctional protein that possesses ion channel (IC) activity, an important ... [+]
Deletion of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) envelope (E) gene attenuates the virus. E gene
encodes a small multifunctional protein that possesses ion channel (IC) activity, an important function in virus-host
interaction. To test the contribution of E protein IC activity in virus pathogenesis, two recombinant mouse-adapted SARSCoVs,
each containing one single amino acid mutation that suppressed ion conductivity, were engineered. After serial
infections, mutant viruses, in general, incorporated compensatory mutations within E gene that rendered active ion
channels. Furthermore, IC activity conferred better fitness in competition assays, suggesting that ion conductivity represents
an advantage for the virus. Interestingly, mice infected with viruses displaying E protein IC activity, either with the wild-type
E protein sequence or with the revertants that restored ion transport, rapidly lost weight and died. In contrast, mice infected
with mutants lacking IC activity, which did not incorporate mutations within E gene during the experiment, recovered from
disease and most survived. Knocking down E protein IC activity did not significantly affect virus growth in infected mice but
decreased edema accumulation, the major determinant of acute respiratory distress syndrome (ARDS) leading to death.
Reduced edema correlated with lung epithelia integrity and proper localization of Na+
/K+ ATPase, which participates in
edema resolution. Levels of inflammasome-activated IL-1b were reduced in the lung airways of the animals infected with
viruses lacking E protein IC activity, indicating that E protein IC function is required for inflammasome activation. Reduction
of IL-1b was accompanied by diminished amounts of TNF and IL-6 in the absence of E protein ion conductivity. All these key
cytokines promote the progression of lung damage and ARDS pathology. In conclusion, E protein IC activity represents a
new determinant for SARS-CoV virulence. [-]
Publicat a
PLOS Pathogens, May 2014, Volume 10, Issue 5, e1004077Drets d'accés
info:eu-repo/semantics/openAccess
Apareix a les col.leccions
- FCA_Articles [498]
Els següents fitxers sobre la llicència estan associats a aquest element:
Except where otherwise noted, this item's license is described as © 2014 Nieto-Torres et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.