RNA viruses encode an RNA-dependent RNA polymerase (RdRp), which is essential for transcription and replication of their genome since host cells lack equivalent enzymes. RdRp residues were shown to be phosphorylated by host kinases in several human, animal or plant viruses including flaviviruses, picornaviruses, coronaviruses, influenza viruses and tymoviruses. RdRps can be phosphorylated on several residues by distinct host kinases. Phosphomimetic mutations of identified phosphorylated residues either positively or negatively regulate RNA synthesis or association of RdRps with RNA or other proteins. Interestingly, some RdRps evolved to recruit cellular kinases through direct protein-protein interaction, likely to promote or to tightly control their own phosphorylation. Given the essential nature of RdRps for RNA virus replication, a better knowledge of RdRps’ phosphorylation is expected to facilitate the design of future drugs that strongly affect polymerase activity.
Background: The relationship between the driving pressure of the respiratory system (ΔPrs) under mechanical ventilation and worse outcome has never been studied specifically in chest trauma patients. The objective of the present study was to assess in cases of chest trauma the relationship between ΔPrs and severity of acute respiratory distress syndrome (ARDS) or death and length of stay. Methods: A retrospective analysis of severe trauma patients (ISS >15) with chest injuries admitted to the Trauma Center from January 2010 to December 2018 was performed. Patients who received mechanical ventilation were included in our analysis. Mechanical ventilation parameters and ΔPrs were recorded during the stay in the intensive care unit. Association of ΔPrs and ARDS with mortality and outcomes was specifically studied at the onset of ARDS (ΔPrs-ARDS) by receiver operator characteristic curve analysis, Kaplan-Meier curves and multivariate analysis.Results: Among the 266 chest trauma patients studied, 194 (73%) developed ARDS. ΔPrs was significantly higher in the ARDS group versus in the no ARDS group (11.6±2.4 cm H2O vs 10.9±1.9 cm H2O, p=0.04). Among the patients with ARDS, no difference according to the duration of mechanical ventilation was found between the high ΔPrs group (ΔPrs-ARDS >14 cm H2O) and the low ΔPrs group (ΔPrs-ARDS ≤14 cm H2O), (p=0.75). ΔPrs-ARDS was not independently associated with the duration of mechanical ventilation (hazard ratio [HR], 1.006; 95% CI, 0.95–1.07; p=0.8) or mortality (HR, 1.07; 95% CI, 0.9–1.28; p=0.45).Conclusion: A high ΔPrs-ARDS was not significantly associated with an increase in mechanical ventilation duration or mortality risk in ARDS patients with chest trauma in contrast with medical patients.
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