title: α1-Antitrypsin reduces rhinovirus infection in primary human airway epithelial cells exposed to cigarette smoke.
abstract: Human rhinovirus (HRV) infections target airway epithelium and are the leading cause of acute exacerbations of COPD. Cigarette smoke (CS) increases the severity of viral infections, but there is no effective therapy for HRV infection. We determined whether α1-antitrypsin (A1AT) reduces HRV-16 infection in CS-exposed primary human airway epithelial cells. Brushed bronchial epithelial cells from normal subjects and patients diagnosed with COPD were cultured at air-liquid interface to induce mucociliary differentiation. These cells were treated with A1AT or bovine serum albumin for 2 hours and then exposed to air or whole cigarette smoke (WCS) with or without HRV-16 (5×10(4) 50% Tissue Culture Infective Dose [TCID50]/transwell) infection for 24 hours. WCS exposure significantly increased viral load by an average of fivefold and decreased the expression of antiviral genes interferon-λ1, OAS1, and MX1. When A1AT was added to WCS-exposed cells, viral load significantly decreased by an average of 29-fold. HRV-16 infection significantly increased HRV-16 receptor intercellular adhesion molecule-1 messenger RNA expression in air-exposed cells, which was decreased by A1AT. A1AT-mediated reduction of viral load was not accompanied by increased epithelial antiviral gene expression or by inhibiting the activity of 3C protease involved in viral replication or maturation. Our findings demonstrate that A1AT treatment prevents a WCS-induced increase in viral load and for the first time suggest a therapeutic effect of A1AT on HRV infection.
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: Reena
authors.initials: R
authors.lastname: Berman
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: Di
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Chu
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000821:virology; D016022:Case-Control Studies; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000821:virology; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010850:Picornaviridae Infections / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000821:virology; D012141:Respiratory Tract Infections / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D012229:Rhinovirus / Q000187:drug effects* / Q000472:pathogenicity; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D019562:Viral Load; D000515:alpha 1-Antitrypsin / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; C573420:ICAM1 protein, human; D012906:Smoke; D000515:alpha 1-Antitrypsin; D018799:Intercellular Adhesion Molecule-1
keywords: COPD; ICAM-1; cigarette smoke; rhinovirus; α1-antitrypsin