scholarly journals IRF7 Is Required for the Second Phase Interferon Induction during Influenza Virus Infection in Human Lung Epithelia

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 377 ◽  
Author(s):  
Wenxin Wu ◽  
Wei Zhang ◽  
Lili Tian ◽  
Brent R. Brown ◽  
Matthew S. Walters ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Cell Line ◽  
Human Lung ◽  
De Novo ◽  
Influenza Virus Infection ◽  
Alveolar Epithelial Cells ◽  
Epithelial Cell Line ◽  
Second Phase ◽  
Alveolar Epithelial

Influenza A virus (IAV) infection is a major cause of morbidity and mortality. Retinoic acid-inducible protein I (RIG-I) plays an important role in the recognition of IAV in most cell types, and leads to the activation of interferon (IFN). We investigated mechanisms of RIG-I and IFN induction by IAV in the BCi-NS1.1 immortalized human airway basal cell line and in the A549 human alveolar epithelial cell line. We found that the basal expression levels of RIG-I and regulatory transcription factor (IRF) 7 were very low in BCi-NS1.1 cells. IAV infection induced robust RIG-I and IRF7, not IRF3, expression. siRNA against IRF7 and mitochondrial antiviral-signaling protein (MAVS), but not IRF3, significantly inhibited RIG-I mRNA expression and IFN induction by IAV infection. Most importantly, even without virus infection, IFN-β alone induced RIG-I, and siRNA against IRF7 did not inhibit RIG-I induction by IFN-β. Similar results were found in the alveolar basal epithelial A549 cell line. RIG-I and IRF7 expression in humans is highly inducible and greatly amplified by IFN produced from virus infected cells. IFN induction can be separated into two phases, that initially induced by the virus with basal RIG-I (the first phase), and that induced by the subsequent virus with amplified RIG-I from the first phase IFN (the second phase). The de novo synthesis of IRF7 is required for the second phase IFN induction during influenza virus infection in human lung bronchial and alveolar epithelial cells.

scholarly journals Differential Susceptibilities of Human Lung Primary Cells to H1N1 Influenza Viruses

2015 ◽  
Vol 89 (23) ◽  
pp. 11935-11944 ◽  
Author(s):  
Emily Travanty ◽  
Bin Zhou ◽  
Hongbo Zhang ◽  
Y. Peter Di ◽  
John F. Alcorn ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Human Lung ◽  
Influenza Virus Infection ◽  
Alveolar Epithelial Cells ◽  
Host Susceptibility ◽  
Epithelial Barrier ◽  
Primary Cells ◽  
Alveolar Epithelial ◽  
Increased Susceptibility ◽  
Human Alveolar Epithelial Cells

ABSTRACTHuman alveolar epithelial cells (AECs) and alveolar macrophages (AMs) are the first lines of lung defense. Here, we report that AECs are the direct targets for H1N1 viruses that have circulated since the 2009 pandemic (H1N1pdm09). AMs are less susceptible to H1N1pdm09 virus, but they produce significantly more inflammatory cytokines than AECs from the same donor. AECs form an intact epithelial barrier that is destroyed by H1N1pdm09 infection. However, there is significant variation in the cellular permissiveness to H1N1pdm09 infection among different donors. AECs from obese donors appear to be more susceptible to H1N1pdm09 infection, whereas gender, smoking history, and age do not appear to affect AEC susceptibility. There is also a difference in response to different strains of H1N1pdm09 viruses. Compared to A/California04/09 (CA04), A/New York/1682/09 (NY1682) is more infectious and causes more epithelial barrier injury, although it stimulates less cytokine production. We further determined that a single amino acid residue substitution in NY1682 hemagglutinin is responsible for the difference in infectivity. In conclusion, this is the first study of host susceptibility of human lung primary cells and the integrity of the alveolar epithelial barrier to influenza. Further elucidation of the mechanism of increased susceptibility of AECs from obese subjects may facilitate the development of novel protection strategies against influenza virus infection.IMPORTANCEDisease susceptibility of influenza is determined by host and viral factors. Human alveolar epithelial cells (AECs) form the key line of lung defenses against pathogens. Using primary AECs from different donors, we provided cellular level evidence that obesity might be a risk factor for increased susceptibility to influenza. We also compared the infections of two closely related 2009 pandemic H1N1 strains in AECs from the same donor and identified a key viral factor that affected host susceptibility, the dominance of which may be correlated with disease epidemiology. In addition, primary human AECs can serve as a convenient and powerful model to investigate the mechanism of influenza-induced lung injury and determine the effect of genetic and epigenetic factors on host susceptibility to pandemic influenza virus infection.

scholarly journals Alveolar Epithelial Cells Direct Monocyte Transepithelial Migration upon Influenza Virus Infection: Impact of Chemokines and Adhesion Molecules

2006 ◽  
Vol 177 (3) ◽  
pp. 1817-1824 ◽  
Author(s):  
Susanne Herold ◽  
Werner von Wulffen ◽  
Mirko Steinmueller ◽  
Stephan Pleschka ◽  
William A. Kuziel ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Epithelial Cells ◽  
Virus Infection ◽  
Adhesion Molecules ◽  
Influenza Virus Infection ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial

Progranulin aggravates pulmonary immunopathology during influenza virus infection

Thorax ◽  
2018 ◽  
Vol 74 (3) ◽  
pp. 305-308 ◽  
Author(s):  
Qin Luo ◽  
Xingxing Yan ◽  
Hongmei Tu ◽  
Yibing Yin ◽  
Ju Cao
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Inflammatory Diseases ◽  
Influenza Virus Infection ◽  
Epithelial Barrier ◽  
Alveolar Epithelial ◽  
Cytokines And Chemokines ◽  
Deficient Mice ◽  
Experimental Influenza

Progranulin (PGRN) exerts multiple functions in various inflammatory diseases. However, the role of PGRN in the pathogenesis of virus infection is unknown. Here, we demonstrated that PGRN production was up-regulated in clinical and experimental influenza, which contributed to the deleterious inflammatory response after influenza virus infection in mice. PGRN-deficient mice were protected from influenza virus-induced lung injury and mortality. Decreased mortality was associated with significantly reduced influx of neutrophils and monocytes/macrophages, release of cytokines and chemokines, and permeability of the alveolar–epithelial barrier without affecting viral clearance. Our findings suggest that PGRN exacerbates pulmonary immunopathology during influenza virus infection.

scholarly journals Influenza virus infection alters ion channel function of airway and alveolar cells: mechanisms and physiological sequelae

2017 ◽  
Vol 313 (5) ◽  
pp. L845-L858 ◽  
Author(s):  
James David Londino ◽  
Ahmed Lazrak ◽  
James F. Collawn ◽  
Zsuzsanna Bebok ◽  
Kevin S. Harrod ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Bacterial Infections ◽  
Alveolar Epithelial Cell ◽  
Ionic Composition ◽  
Influenza Virus Infection ◽  
Alveolar Epithelial Cells ◽  
Alveolar Cells ◽  
Alveolar Epithelial

The cystic fibrosis transmembrane conductance regulator (CFTR) and the amiloride-sensitive epithelial sodium channels (ENaC) are located in the apical membranes of airway and alveolar epithelial cells. These transporters play an important role in the regulation of lung fluid balance across airway and alveolar epithelia by being the conduits for chloride (Cl−) and bicarbonate ([Formula: see text]) secretion and sodium (Na+) ion absorption, respectively. The functional role of these channels in the respiratory tract is to maintain the optimum volume and ionic composition of the bronchial periciliary fluid (PCL) and alveolar lining fluid (ALF) layers. The PCL is required for proper mucociliary clearance of pathogens and debris, and the ALF is necessary for surfactant homeostasis and optimum gas exchange. Dysregulation of ion transport may lead to mucus accumulation, bacterial infections, inflammation, pulmonary edema, and compromised respiratory function. Influenza (or flu) in mammals is caused by influenza A and B viruses. Symptoms include dry cough, sore throat, and is often followed by secondary bacterial infections, accumulation of fluid in the alveolar spaces and acute lung injury. The underlying mechanisms of flu symptoms are not fully understood. This review summarizes our present knowledge of how influenza virus infections alter airway and alveolar epithelial cell CFTR and ENaC function in vivo and in vitro and the role of these changes in influenza pathogenesis.

scholarly journals Influenza virus-induced lung injury: pathogenesis and implications for treatment

2015 ◽  
Vol 45 (5) ◽  
pp. 1463-1478 ◽  
Author(s):  
Susanne Herold ◽  
Christin Becker ◽  
Karen M. Ridge ◽  
G.R. Scott Budinger
Keyword(s):  
Influenza Virus ◽  
Lung Injury ◽  
Influenza Virus Infection ◽  
Alveolar Epithelium ◽  
Influenza Viruses ◽  
Viral Clearance ◽  
Alveolar Epithelial Cells ◽  
Human Pathogens ◽  
Alveolar Epithelial ◽  
Molecular Events

The influenza viruses are some of the most important human pathogens, causing substantial seasonal and pandemic morbidity and mortality. In humans, infection of the lower respiratory tract of can result in flooding of the alveolar compartment, development of acute respiratory distress syndrome and death from respiratory failure. Influenza-mediated damage of the airway, alveolar epithelium and alveolar endothelium results from a combination of: 1) intrinsic viral pathogenicity, attributable to its tropism for host airway and alveolar epithelial cells; and 2) a robust host innate immune response, which, while contributing to viral clearance, can worsen the severity of lung injury. In this review, we summarise the molecular events at the virus–host interface during influenza virus infection, highlighting some of the important cellular responses. We discuss immune-mediated viral clearance, the mechanisms promoting or perpetuating lung injury, lung regeneration after influenza-induced injury, and recent advances in influenza prevention and therapy.

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