ICAM1 regulates influenza A survival in lung epithelial cells during the early stages of infection.
Othumpangat-S; Noti-J; Beezhold-D
FASEB J 2014 Apr; 28(1)(Suppl):796.5
Intercellular cell adhesion molecule-1 (CD54 or ICAM-1) is an inducible cell surface glycoprotein that is expressed at low levels on many cell types including leukocytes and endothelial cells. ICAM-1 is known to serve as a receptor for rhinovirus. In this study, we examined the role of ICAM-1 as a signaling molecule in cell survival during the early stages of influenza A infection. Exposure of A549 cells to influenza A induced 100 fold increase in ICAM1 mRNA. The specificity of this response was shown by depleting ICAM1 on the A549 cells by transfecting the cells with siRNA specific for ICAM and then exposing these cells to influenza A. Lack of ICAM1 resulted in increased influenza A copy number. Next we used ICAM1 antibody to inhibit endogenous ICAM1 which resulted in increased infection efficiency of influenza A, suggesting that the lack of ICAM1 in cells is favorable for viral replication. The tissue tropism and virus specificity in inducing ICAM1 was tested by employing different cell lines representing the human respiratory tract and using strains of influenza (H1N1, H3N2, H9N1). Early stage infection with all three strains of influenza significantly increased ICAM1 mRNA, irrespective of the cell origin. Influenza A infection in A549 cells resulted in up-regulation of NF-kB signaling. In conclusion, in lung epithelial cells induced ICAM1 plays a key role in disrupting the viral replication efficiency possibly through the NF-kB pathway.
Viral-diseases; Viral-infections; Respiratory-system-disorders; Respiratory-infections; Lung-cells; Cell-cultures; Cell-function; Cellular-reactions; Leukocytes; Glycoproteins; Proteins; Ribonucleic-acids; Exposure-assessment; Analytical-processes; Antibody-response
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