Lentivirus Vectors Pseudotyped with Filoviral Envelope Glycoproteins Transduce Airway Epithelia from the Apical Surface Independently of Folate Receptor Alpha

• DOI: 10.1128/jvi.77.10.5902-5910.2003
• Publication Date: 2003-04-28T18:43:45Z
• Authors: Patrick L. Sinn; Melissa A. Hickey; Patrick D. Staber; Douglas E. Dylla; Scott A. Jeffers; Beverly L. Davidson; David A. Sanders; Paul B. McCray
• Keywords: 0303 health sciences; Folate Receptors, GPI-Anchored; Genetic Vectors; Respiratory System; Cell Polarity; Epithelial Cells; Receptors, Cell Surface; Immunodeficiency Virus, Feline; Filoviridae; 3. Good health; 03 medical and health sciences; Viral Envelope Proteins; Transduction, Genetic; Cats; Animals; Humans; Carrier Proteins; Cells, Cultured

The practical application of gene therapy as a treatment for cystic fibrosis is limited by poor transfer efficiency with vectors applied to the apical surface airway epithelia. Recently, folate receptor alpha (FR alpha), glycosylphosphatidylinositol-linked protein, was reported be cellular filoviruses. We found that polarized human epithelia expressed abundant FR on their surface. In an attempt target these receptors, we pseudotyped feline immunodeficiency virus (FIV)-based using envelope glycoproteins (GPs) from filoviruses Marburg and Ebola virus. Importantly, primary cultures well-differentiated were transduced when filovirus GP-pseudotyped FIV Furthermore, deleting heavily O-glycosylated extracellular domain GP, improved titer concentrated vector severalfold. To investigate dependence pseudotypes, compared in immortalized epithelium cell lines cultures. By utilizing phosphatidylinositol-specific phospholipase C (PI-PLC) alpha-blocking antibodies, demonstrated alpha-dependent -independent entry glycoprotein-pseudotyped FIV-based Of particular interest, independent observed Understanding viral binding pathways fundamental developing applications.