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Journal of Virology, October 2005, p. 12818-12827, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12818-12827.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Persistent Gene Expression in Mouse Nasal Epithelia following Feline Immunodeficiency Virus-Based Vector Gene Transfer

Patrick L. Sinn,1 Erin R. Burnight,1 Melissa A. Hickey,1 Gary W. Blissard,2 and Paul B. McCray Jr.1*

Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242,1 Boyce Thompson Institute, Cornell University, Ithaca, New York 148532

Received 28 April 2005/ Accepted 22 July 2005

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 106 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 107 to 109 TU/ml. Of note, GP64 from Autographa californica multicapsid nucleopolyhedrovirus resulted in high-titer FIV preparations (~109 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.

* Corresponding author. Mailing address: Department of Pediatrics, Carver College of Medicine, The University of Iowa, 240G EMRB, Iowa City, IA 52242. Phone: (319) 356-4866. Fax: (319) 335-6925. E-mail: paul-mccray{at}uiowa.edu.

Journal of Virology, October 2005, p. 12818-12827, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12818-12827.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sinn, P. L., Arias, A. C., Brogden, K. A., McCray, P. B. Jr. (2008). Lentivirus Vector Can Be Readministered to Nasal Epithelia without Blocking Immune Responses. J. Virol. 82: 10684-10692 [Abstract] [Full Text]  
  • Zhou, J., Blissard, G. W. (2008). Identification of a GP64 Subdomain Involved in Receptor Binding by Budded Virions of the Baculovirus Autographica californica Multicapsid Nucleopolyhedrovirus. J. Virol. 82: 4449-4460 [Abstract] [Full Text]  
  • Hendrickson, B., Senadheera, D., Mishra, S., Bui, K. C. T., Wang, X., Chan, B., Petersen, D., Pepper, K., Lutzko, C. (2007). Development of Lentiviral Vectors with Regulated Respiratory Epithelial Expression In Vivo. Am. J. Respir. Cell Mol. Bio. 37: 414-423 [Abstract] [Full Text]  


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