Abstract
The human severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly infectious virus that causes severe respiratory infections in humans. The spike envelope glycoprotein of SARS-CoV, the main determinant of SARS-CoV tropism, was isolated and used to pseudotype a human immunodeficiency virus (HTV)-based vector. Spike-pseudotyped HIV vector was generated and evaluated in vitro on well-differentiated human airway epithelial cells and bronchial explants and in vivo in murine airways. The spike envelope was less efficient at promoting HIV vector transduction of murine airway epithelium than an optimized deletion mutant of the Zaire ebolavirus envelope glycoprotein (NTD6L), which was used as a benchmark. However, spike-pseudotyped HIV vector was substantially more efficient than NTD6L-pseudotyped vector on human airway epithelium as demonstrated by lacZ gene transfer in primary cultures of epithelial cells and bronchial explants. In addition, this study shows that spike-pseudotyped HIV-based vector can efficiently transduce human dendritic cells and epithelial cells of the esophagus, which may have implications in investigating mechanisms of SARS-CoV pathogenesis. Spike-pseudotyped HTV-based vector is a novel lung-directed gene transfer vehicle that holds promise for the treatment of genetic lung diseases such as cystic fibrosis or α1-antitrypsin deficiency.
Original language | English (US) |
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Pages (from-to) | 413-422 |
Number of pages | 10 |
Journal | Human Gene Therapy |
Volume | 18 |
Issue number | 5 |
DOIs | |
State | Published - May 2007 |
Externally published | Yes |
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Genetics