sidestream smoke exposure increases the susceptibility of airway epithelia to adenoviral infection侧流烟烟雾暴露增加气道上皮细胞adenoviral感染的易感性.pdfVIP

Sidestream Smoke Exposure Increases the Susceptibility of Airway Epithelia to Adenoviral Infection 1 1 2 2 Priyanka Sharma , Abimbola O. Kolawole , Susan B. Core , Adriana E. Kajon *, Katherine J. D. A. Excoffon1* 1 Department of Biological Sciences, Wright State University, Dayton, Ohio, United States of America, 2 Infectious Disease Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico, United States of America Abstract Background: Although significant epidemiological evidence indicates that cigarette smoke exposure increases the incidence and severity of viral infection, the molecular mechanisms behind the increased susceptibility of the respiratory tract to viral pathogens are unclear. Adenoviruses are non-enveloped DNA viruses and important causative agents of acute respiratory disease. The Coxsackievirus and adenovirus receptor (CAR) is the primary receptor for many adenoviruses. We hypothesized that cigarette smoke exposure increases epithelial susceptibility to adenovirus infection by increasing the abundance of apical CAR. Methodology and Findings: Cultured human airway epithelial cells (CaLu-3) were used as a model to investigate the effect of sidestream cigarette smoke (SSS), mainstream cigarette smoke (MSS), or control air exposure on the susceptibility of polarized respiratory epithelia to adenoviral infection. Using a Cultex air-liquid interface exposure system, we have discovered novel differences in epithelial susceptibility between SSS and MSS exposures. SSS exposure upregulates an eight-exon isoform of CAR and increases adenoviral entry from the apical surface whilst MSS exposure is similar to control