Journal article
Lack of high affinity fiber receptor activity explains the resistance of ciliated airway epithelia to adenovirus infection
The Journal of clinical investigation, Vol.100(5), pp.1144-1149
09/01/1997
DOI: 10.1172/JCI119625
PMCID: PMC508289
PMID: 9276731
Abstract
Although recombinant adenoviruses are attractive vectors for gene transfer to airway epithelia, they have proven to be relatively inefficient. To investigate the mechanisms of adenovirus-mediated gene transfer to airway epithelia, we examined the role of adenovirus fiber and penton base, the two proteins involved in attachment to and entry of virus into the cell. We used human airway epithelia grown under conditions that allow differentiation and development of a ciliated apical surface that closely resembles the in vivo condition. We found that addition of fiber protein inhibited virus binding and vector-mediated gene transfer to immature airway epithelia, as well as to primary cultures of rat hepatocytes and HeLa cells. However, fiber protein had no effect on vector binding and gene transfer to ciliated airway epithelia. We obtained similar results with addition of penton base protein: the protein inhibited gene transfer to immature epithelia, whereas there was no effect with ciliated epithelia. Moreover, infection was not attenuated with an adenovirus containing a mutation in penton base that prevents the interaction with cell surface integrins. These data suggest that the receptors required for efficient infection by adenovirus are either not present or not available on the apical surface of ciliated human airway epithelia. The results explain the reason for inefficient gene transfer and suggest approaches for improvement.
Details
- Title: Subtitle
- Lack of high affinity fiber receptor activity explains the resistance of ciliated airway epithelia to adenovirus infection
- Creators
- Joseph Zabner - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 5224Paul Freimuth - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 5224Aurita Puga - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 5224Alfredo Fabrega - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 5224Michael J Welsh - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 5224
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.100(5), pp.1144-1149
- DOI
- 10.1172/JCI119625
- PMID
- 9276731
- PMCID
- PMC508289
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 09/01/1997
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9984013918702771
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