Role of latent viral infections in chronic obstructive pulmonary disease and asthma.
Acute viral respiratory tract infections are well known to precipitate asthma attacks and acute exacerbations of chronic obstructive pulmonary disease, but their role in the pathogenesis of chronic disease is poorly defined. Double-stranded DNA viruses have the ability to persist in airway epithelial cells long after the acute infection has cleared. During these latent infections, viral genes are expressed at the protein level without replication of a complete virus. The expression of the adenoviral trans-activating protein has been demonstrated in the airway epithelium of both human and animal lungs and is associated with an amplification of the cigarette smoke-induced inflammatory response. Studies of cultured human airway epithelial cells have also shown that transfection with this viral gene upregulates the expression of intercellular adhesion molecule 1 and interleukin 8 by these cells when they are challenged with endotoxin. In guinea pigs, cigarette smoke-induced emphysema is amplified by latent adenoviral infection. Furthermore, this infection independently increased the number of CD-8 cells, whereas the cigarette smoke independently increased the number of CD-4 cells in the inflammatory infiltrate. On the other hand, allergen-induced lung inflammation was uninfluenced by latent adenoviral infection in the guinea pig, but the latent infection caused the eosinophilic component of this response to become steroid resistant. These studies suggest that latent adenoviral infections may have a role in the pathogenesis of obstructive airway disease by amplifying the response to cigarette smoke and inducing steroid resistance.
Hogg
J C
JC
University of British Columbia McDonald Research Laboratory/iCAPTURE Centre, St. Paul's Hospital, Vancouver, British Columbia, Canada. jhogg@mrl.ubc.ca
D000256:Adenoviridae / Q000235:genetics; D000257:Adenoviridae Infections / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D000328:Adult; D000485:Allergens; D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000276:immunology; D001988:Bronchiolitis / Q000150:complications / Q000175:diagnosis; D001992:Bronchoalveolar Lavage Fluid; D002648:Child; D004279:DNA, Viral; D005500:Follow-Up Studies; D006168:Guinea Pigs; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D008173:Lung Diseases, Obstructive / Q000209:etiology* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011656:Pulmonary Emphysema / Q000209:etiology; D012135:Respiratory Sounds; D012141:Respiratory Tract Infections / Q000150:complications* / Q000175:diagnosis; D012307:Risk Factors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D014162:Transfection; D015854:Up-Regulation; D014764:Viral Proteins
D000485:Allergens; D004279:DNA, Viral; D014028:Tobacco Smoke Pollution; D014764:Viral Proteins