Journal article
Gene transfer to respiratory epithelia with lentivirus pseudotyped with jaagsiekte sheep retrovirus envelope glycoprotein
Human gene therapy, Vol.16(4), pp.479-488
2005
DOI: 10.1089/hum.2005.16.479
PMID: 15871679
Abstract
A feline immunodeficiency virus (FIV)-based lentiviral vector was pseudotyped to identify envelope (env) glycoproteins that direct efficient gene transfer to pulmonary epithelia for the treatment or prevention of lung diseases. The envelope glycoprotein from the Jaagsiekte sheep retrovirus (JSRV) is a candidate under investigation. We utilized high titer FIV vector (>10(8) TU/ml) pseudotyped with the JSRV env glycoprotein (JSRVFIV) to study the transduction of polarized primary cultures of human airway epithelia and receptor/vector interactions. The reported receptor for JSRV, hyaluronidase 2 (HYAL2), is a GPI-linked protein. We expressed FLAG-tagged HYAL2 in polarized airway epithelia using an adenoviral vector and documented that the HYAL2 protein sorts predominantly to the apical surface. Of interest, the efficiency of gene transfer with apically applied JSRV-FIV was markedly less than FIV pseudotyped with VSV-G, even in Ad-HYAL2 complemented epithelia. The inefficient gene transfer with JSRV-FIV in HYAL2 complemented cells suggests that factors other than receptor abundance limit apical gene transfer efficiency with this envelope. JSRV-FIV transduced the distal lung epithelia of rabbits in vivo and transduced primary cultures of rabbit type II cells with 100-fold greater efficiency than primary cultures of rabbit tracheal cells. These data indicate that a lentivirus pseudotyped with the JSRV envelope glycoprotein transduces type II cells with greater efficiency than conducting airway epithelia and provides an example of glycoprotein-mediated cell-specific tropism within a tissue with a widely heterogeneous cell population.
Details
- Title: Subtitle
- Gene transfer to respiratory epithelia with lentivirus pseudotyped with jaagsiekte sheep retrovirus envelope glycoprotein
- Creators
- Patrick L SINN - Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, United StatesAndrea K PENISTEN - Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, United StatesErin R BURNIGHT - Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, United StatesMelissa A HICKEY - Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, United StatesGreg WILLIAMS - Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, United StatesDiann M MCCOY - Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, United StatesRama K MALLAMPALLI - Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, United StatesPaul B MCCRAY - Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, United States
- Resource Type
- Journal article
- Publication Details
- Human gene therapy, Vol.16(4), pp.479-488
- Publisher
- Liebert
- DOI
- 10.1089/hum.2005.16.479
- PMID
- 15871679
- ISSN
- 1043-0342
- eISSN
- 1557-7422
- Language
- English
- Date published
- 2005
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9984093342102771
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