scholarly journals Hypercytokinemia and Hyperactivation of Phospho-p38 Mitogen-Activated Protein Kinase in Severe Human Influenza A Virus Infection

2007 ◽  
Vol 45 (6) ◽  
pp. 723-731 ◽  
Author(s):  
N. Lee ◽  
C. K. Wong ◽  
P. K. S. Chan ◽  
S. W. M. Lun ◽  
G. Lui ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Mitogen Activated Protein Kinase ◽  
Human Influenza ◽  
Mitogen Activated Protein ◽  
Influenza A Virus Infection

scholarly journals Modification of the Ferret Model for Pneumonia From Seasonal Human Influenza A Virus Infection

2012 ◽  
Vol 49 (3) ◽  
pp. 562-568 ◽  
Author(s):  
J. M. A. van den Brand ◽  
K. J. Stittelaar ◽  
L. M. E. Leijten ◽  
G. van Amerongen ◽  
J. H. Simon ◽  
...  
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Human Influenza ◽  
Influenza A Virus Infection

scholarly journals In Vitro Inhibition of Human Influenza A Virus Infection by Fruit-Juice Concentrate of Japanese Plum (Prunus mume SIEB. et ZUCC)

2008 ◽  
Vol 31 (3) ◽  
pp. 511-515 ◽  
Author(s):  
Sangchai Yingsakmongkon ◽  
Daisei Miyamoto ◽  
Nongluk Sriwilaijaroen ◽  
Kimie Fujita ◽  
Kosai Matsumoto ◽  
...  
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Fruit Juice ◽  
Prunus Mume ◽  
Human Influenza ◽  
Juice Concentrate ◽  
Influenza A Virus Infection ◽  
In Vitro Inhibition

scholarly journals Inhibiting Protein Kinase D Promotes Airway Epithelial Barrier Integrity in Mouse Models of Influenza A Virus Infection

2020 ◽  
Vol 11 ◽  
Author(s):  
Janelle M. Veazey ◽  
Sophia I Eliseeva ◽  
Sara E. Hillman ◽  
Kristie Stiles ◽  
Timothy R. Smyth ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Epithelial Cells ◽  
Virus Infection ◽  
Signaling Pathways ◽  
Influenza A Virus ◽  
Influenza A ◽  
Protein Kinase D ◽  
Double Stranded Rna ◽  
Barrier Integrity ◽  
Influenza A Virus Infection

RationaleProtein kinase D (PKD) is a serine/threonine kinase family that is involved in a wide array of signaling pathways. Although PKD has been implicated in immune responses, relatively little is known about the function of PKD in the lung or during viral infections.ObjectivesWe investigated the hypothesis that PKD is involved in multiple aspects of host response to viral infection.MethodsThe selective PKD inhibitor CRT0010166 was administered to C57BL/6 mice prior to and during challenge with either inhaled double-stranded RNA or Influenza A Virus. PKD signaling pathways were investigated in human bronchial epithelial cells treated with CRT0010166, double-stranded RNA, and/or infected with Influenza A Virus.MeasurementsTotal protein and albumin accumulation in the bronchoalveolar fluid was used to asses inside/out leak. Clearance of inhaled FITC-dextran out of the airspace was used to assess outside/in leak. Cytokines and neutrophils in bronchoalveolar lavage were assayed with ELISAs and cytospins respectively. Viral RNA level was assessed with RT-PCR and protein level assessed by ELISA.Main ResultsPKD inhibition prevented airway barrier dysfunction and pro-inflammatory cytokine release. Epithelial cells express PKD3, and PKD3 siRNA knock-down inhibited polyI:C induced cytokine production. Lung epithelial-specific deletion of PKD3 (CC10-Cre x PKD3-floxed mice) partially attenuated polyI:C-induced barrier disruption in vivo. Mechanistically, we found that PKD promoted cytokine mRNA transcription, not secretion, likely through activating the transcription factor Sp1. Finally, prophylactic CRT treatment of mice promoted barrier integrity during influenza virus infection and reduced viral burden.ConclusionsInhibiting PKD promotes barrier integrity, limit pathogenic cytokine levels, and restrict Influenza A Virus infection. Therefore, PKD is an attractive target for novel antiviral therapeutics.

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