Cigarette smoke alters respiratory syncytial virus-induced apoptosis and replication

Dayna J Groskreutz; Martha M Monick; Ellen C Babor; Toru Nyunoya; Steven M Varga; Dwight C Look; Gary W Hunninghake

doi:10.1165/rcmb.2008-0131OC

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Cigarette smoke alters respiratory syncytial virus-induced apoptosis and replication

Journal article

Open access

Peer reviewed

Cigarette smoke alters respiratory syncytial virus-induced apoptosis and replication

Dayna J Groskreutz, Martha M Monick, Ellen C Babor, Toru Nyunoya, Steven M Varga, Dwight C Look and Gary W Hunninghake

American journal of respiratory cell and molecular biology, Vol.41(2), pp.189-198

08/2009

DOI: 10.1165/rcmb.2008-0131OC

PMCID: PMC2715908

PMID: 19131644

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https://doi.org/10.1165/rcmb.2008-0131OCView

Published (Version of record) Open Access

Abstract

Individuals exposed to cigarette smoke have a greater number and severity of viral infections, including respiratory syncytial virus (RSV) infections, than do nonsmokers, but the cellular mechanism is unknown. Our objective was to determine the mechanism by which cigarette smoke augments viral infection. We hypothesize that cigarette smoke causes necrosis and prevents virus-induced cellular apoptosis, and that this is associated with increased inflammation and viral replication. Primary airway epithelial cells were exposed to cigarette smoke extract for 2 days, followed by 1 day of RSV exposure. Western blot detection of cleaved caspases 3 and 7 showed less apoptosis when cells were treated with cigarette smoke before viral infection. This finding was confirmed with ELISA and TUNEL detection of apoptosis. Measures of cell viability, including propidium iodide staining, ATP assay, and cell counts, indicated that cigarette smoke causes necrosis rather than virus-induced apoptosis. Using plaque assay and fluorescently-labeled RSV, we showed that although there were less live cells in the cigarette smoke-pretreated group, viral load was increased. The effect was inhibited by pretreatment of cells with N-acetylcysteine and aldehyde dehydrogenase, suggesting that the effect was primarily mediated by reactive aldehydes. Cigarette smoke causes necrosis rather than apoptosis in viral infection, resulting in increased inflammation and enhanced viral replication.

Acetylcysteine - metabolism

Animals

Antiviral Agents - metabolism

Apoptosis - drug effects

Apoptosis - physiology

Caspase 3 - metabolism

Caspase 7 - metabolism

Cell Line

Child

Dose-Response Relationship, Drug

Enzyme Activation

Enzyme Inhibitors - metabolism

Epithelial Cells - cytology

Epithelial Cells - drug effects

Epithelial Cells - virology

Female

Humans

Respiratory Mucosa - cytology

Respiratory Mucosa - drug effects

Respiratory Syncytial Virus, Human - drug effects

Respiratory Syncytial Virus, Human - physiology

Smoke

Smoking - adverse effects

Staurosporine - metabolism

Tumor Suppressor Protein p53 - metabolism

Virus Replication - drug effects

X-Linked Inhibitor of Apoptosis Protein - metabolism

Details

Title: Subtitle: Cigarette smoke alters respiratory syncytial virus-induced apoptosis and replication
Creators: Dayna J Groskreutz - Division of Pulmonary, Critical Care, and Occupational Medicine, 100 EMRB, Iowa City, IA 52242, USA. Dayna-Groskreutz@uiowa.edu
Martha M Monick - University of Iowa, Internal Medicine
Ellen C Babor
Toru Nyunoya
Steven M Varga - University of Iowa, Microbiology and Immunology
Dwight C Look
Gary W Hunninghake
Resource Type: Journal article
Publication Details: American journal of respiratory cell and molecular biology, Vol.41(2), pp.189-198
DOI: 10.1165/rcmb.2008-0131OC
PMID: 19131644
PMCID: PMC2715908
NLM abbreviation: Am J Respir Cell Mol Biol
ISSN: 1044-1549
eISSN: 1535-4989
Grant note: HL075559-04 / NHLBI NIH HHS HL077431-01 / NHLBI NIH HHS HL073967-01 / NHLBI NIH HHS K08 HL089392 / NHLBI NIH HHS AI 063520 / NIAID NIH HHS RR00059 / NCRR NIH HHS R01 HL079901 / NHLBI NIH HHS HL089392-02 / NHLBI NIH HHS R01 HL079901-01A1 / NHLBI NIH HHS R01 HL079901-05 / NHLBI NIH HHS
Language: English
Date published: 08/2009
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Graduate College Admin and Gen; Microbiology and Immunology; Pathology; Internal Medicine
Record Identifier: 9984213857802771

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