Human immunodeficiency viral vector pseudotyped with the spike envelope of severe acute respiratory syndrome coronavirus transduces human airway epithelial cells and dendritic cells.
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 (HIV)-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 HIV-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 alpha(1)-antitrypsin deficiency.
Kobinger
Gary P
GP
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada R3E 3R2.
Limberis
Maria P
MP
Somanathan
Suri
S
Schumer
Gregory
G
Bell
Peter
P
Wilson
James M
JM
D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006678:HIV / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D007763:Lac Operon; D008171:Lung Diseases / Q000628:therapy; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D012137:Respiratory System / Q000166:cytology / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics*; D064370:Spike Glycoprotein, Coronavirus; D014161:Transduction, Genetic; D014759:Viral Envelope Proteins / Q000235:genetics*
D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins