Science Inventory

Reduced expression IRF7 in nasal epithelial cells from smokers as a potential mechanism mediating enhanced susceptibility to influenza

Citation:

JASPERS, I., L. BRIGHTON, W. Zhang, J. CARSON, AND T. NOAH. Reduced expression IRF7 in nasal epithelial cells from smokers as a potential mechanism mediating enhanced susceptibility to influenza. Presented at American Thoracic Society Annual Meeting, Toronto, ON, CANADA, May 16 - 28, 2008.

Impact/Purpose:

research results

Description:

Rationale: Smokers are more susceptible to viral infections, including influenza virus, yet the mechanisms mediating this effect are not known. Methods: We have established an in vitro model of differentiated nasal epithelial cells from smokers, which maintain enhanced levels of mucin production, similar to those observed in vivo. These cells were infected with influenza A and examined 24 hrs post-infection. For our in vivo studies, healthy volunteers were inoculated with the live-attenuated influenza virus (LAIV) vaccine and nasal biopsies were obtained before and 4 days after administration of LAIV. Results: Differentiated nasal epithelial cells from smokers respond to influenza infection in vitro with greater cytotoxicity, IL-6 release, and viral shedding. To determine potential mechanisms mediating this enhanced susceptibility, we examined type I interferon (IFN) expression. Influenza-infected nasal epithelial from smokers produced significantly less IFN-alpha as compared to cells from non-smokers. Similarly, expression of IRF7, a key transcription factor controlling the expression of IFN-alpha, was significantly decreased in influenza infected nasal epithelial cells from smokers in vitro. Similarly, preliminary analysis suggests that inoculation with LAIV results in significantly lower expression of IRF7 in nasal biopsies from smokers as compared to those from non-smokers, thus confirming our observations made in vitro. Conclusions: Taken together these data indicate that influenza virus infection results in reduced expression and function of the transcription factor IRF7 in nasal epithelial cells from smokers both in vitro and in vivo. Since this would be predicted to reduce antiviral interferon responses, these data suggest a potential mechanism rendering smokers more susceptible to respiratory viral infection.

Record Details:

Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Product Published Date: 05/16/2008
Record Last Revised: 03/26/2013
OMB Category: Other
Record ID: 188782