Journal article
Lentivirus vectors pseudotyped with filoviral envelope glycoproteins transduce airway epithelia from the apical surface independently of folate receptor alpha
Journal of virology, Vol.77(10), pp.5902-5910
05/2003
DOI: 10.1128/JVI.77.10.5902-5910.2003
PMCID: PMC154009
PMID: 12719583
Abstract
The practical application of gene therapy as a treatment for cystic fibrosis is limited by poor gene transfer efficiency with vectors applied to the apical surface of airway epithelia. Recently, folate receptor alpha (FR alpha), a glycosylphosphatidylinositol-linked surface protein, was reported to be a cellular receptor for the filoviruses. We found that polarized human airway epithelia expressed abundant FR alpha on their apical surface. In an attempt to target these apical receptors, we pseudotyped feline immunodeficiency virus (FIV)-based vectors by using envelope glycoproteins (GPs) from the filoviruses Marburg virus and Ebola virus. Importantly, primary cultures of well-differentiated human airway epithelia were transduced when filovirus GP-pseudotyped FIV was applied to the apical surface. Furthermore, by deleting a heavily O-glycosylated extracellular domain of the Ebola GP, we improved the titer of concentrated vector severalfold. To investigate the folate receptor dependence of gene transfer with the filovirus pseudotypes, we compared gene transfer efficiency in immortalized airway epithelium cell lines and primary cultures. By utilizing phosphatidylinositol-specific phospholipase C (PI-PLC) treatment and FR alpha-blocking antibodies, we demonstrated FR alpha-dependent and -independent entry by filovirus glycoprotein-pseudotyped FIV-based vectors in airway epithelia. Of particular interest, entry independent of FR alpha was observed in primary cultures of human airway epithelia. Understanding viral vector binding and entry pathways is fundamental for developing cystic fibrosis gene therapy applications.
Details
- Title: Subtitle
- Lentivirus vectors pseudotyped with filoviral envelope glycoproteins transduce airway epithelia from the apical surface independently of folate receptor alpha
- Creators
- Patrick L Sinn - Program in Gene Therapy, Department of Pediatrics, University of Iowa College of Medicine, Iowa City, Iowa 52242, USAMelissa A HickeyPatrick D StaberDouglas E DyllaScott A JeffersBeverly L DavidsonDavid A SandersPaul B McCray Jr
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.77(10), pp.5902-5910
- DOI
- 10.1128/JVI.77.10.5902-5910.2003
- PMID
- 12719583
- PMCID
- PMC154009
- NLM abbreviation
- J Virol
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Grant note
- HL-51670 / NHLBI NIH HHS R01 HL-61460 / NHLBI NIH HHS P30 DK-54759 / NIDDK NIH HHS NS-34568 / NINDS NIH HHS F32 HL067623 / NHLBI NIH HHS PPG HL-51670 / OAPP OPHS HHS P01 HL051670 / NHLBI NIH HHS HL-67623 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS R01 NS034568 / NINDS NIH HHS
- Language
- English
- Date published
- 05/2003
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984093324802771
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