Journal article
Persistent Gene Expression in Mouse Nasal Epithelia following Feline Immunodeficiency Virus-Based Vector Gene Transfer
Journal of virology, Vol.79(20), pp.12818-12827
10/2005
DOI: 10.1128/JVI.79.20.12818-12827.2005
PMCID: PMC1235842
PMID: 16188984
Abstract
Gene transfer development for treatment or prevention of cystic fibrosis lung disease has been limited by the inability of vectors to efficiently and persistently transduce airway epithelia. Influenza A is an enveloped virus with natural lung tropism; however, pseudotyping feline immunodeficiency virus (FIV)-based lentiviral vector with the hemagglutinin envelope protein proved unsuccessful. Conversely, pseudotyping FIV with the envelope protein from influenza D (Thogoto virus GP75) resulted in titers of 10
6
transducing units (TU)/ml and conferred apical entry into well-differentiated human airway epithelial cells. Baculovirus GP64 envelope glycoproteins share sequence identity with influenza D GP75 envelope glycoproteins. Pseudotyping FIV with GP64 from three species of baculovirus resulted in titers of 10
7
to 10
9
TU/ml. Of note, GP64 from
Autographa californica
multicapsid nucleopolyhedrovirus resulted in high-titer FIV preparations (∼10
9
TU/ml) and conferred apical entry into polarized primary cultures of human airway epithelia. Using a luciferase reporter gene and bioluminescence imaging, we observed persistent gene expression from in vivo gene transfer in the mouse nose with
A. californica
GP64-pseudotyped FIV (AcGP64-FIV). Longitudinal bioluminescence analysis documented persistent expression in nasal epithelia for ∼1 year without significant decline. According to histological analysis using a LacZ reporter gene, olfactory and respiratory epithelial cells were transduced. In addition, methylcellulose-formulated AcGP64-FIV transduced mouse nasal epithelia with much greater efficiency than similarly formulated vesicular stomatitis virus glycoprotein-pseudotyped FIV. These data suggest that AcGP64-FIV efficiently transduces and persistently expresses a transgene in nasal epithelia in the absence of agents that disrupt the cellular tight junction integrity.
Details
- Title: Subtitle
- Persistent Gene Expression in Mouse Nasal Epithelia following Feline Immunodeficiency Virus-Based Vector Gene Transfer
- Creators
- Patrick L Sinn - Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242Erin R Burnight - Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242Melissa A Hickey - Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242Gary W Blissard - Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242Paul B McCray - Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.79(20), pp.12818-12827
- DOI
- 10.1128/JVI.79.20.12818-12827.2005
- PMID
- 16188984
- PMCID
- PMC1235842
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Publisher
- American Society for Microbiology
- Language
- English
- Date published
- 10/2005
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9984093498302771
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