PMID- 12719583
OWN - NLM
STAT- MEDLINE
DCOM- 20030604
LR  - 20190508
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 77
IP  - 10
DP  - 2003 May
TI  - Lentivirus vectors pseudotyped with filoviral envelope glycoproteins transduce 
      airway epithelia from the apical surface independently of folate receptor alpha.
PG  - 5902-10
AB  - 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.
FAU - Sinn, Patrick L
AU  - Sinn PL
AD  - Program in Gene Therapy, Department of Pediatrics, University of Iowa College of 
      Medicine, Iowa City, Iowa 52242, USA.
FAU - Hickey, Melissa A
AU  - Hickey MA
FAU - Staber, Patrick D
AU  - Staber PD
FAU - Dylla, Douglas E
AU  - Dylla DE
FAU - Jeffers, Scott A
AU  - Jeffers SA
FAU - Davidson, Beverly L
AU  - Davidson BL
FAU - Sanders, David A
AU  - Sanders DA
FAU - McCray, Paul B Jr
AU  - McCray PB Jr
LA  - eng
GR  - P30 DK-54759/DK/NIDDK NIH HHS/United States
GR  - NS-34568/NS/NINDS NIH HHS/United States
GR  - HL-51670/HL/NHLBI NIH HHS/United States
GR  - R01 NS034568/NS/NINDS NIH HHS/United States
GR  - HL-67623/HL/NHLBI NIH HHS/United States
GR  - P01 HL051670/HL/NHLBI NIH HHS/United States
GR  - R01 HL-61460/HL/NHLBI NIH HHS/United States
GR  - PPG HL-51670/PG/OAPP OPHS HHS/United States
GR  - F32 HL067623/HL/NHLBI NIH HHS/United States
GR  - P30 DK054759/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Carrier Proteins)
RN  - 0 (Folate Receptors, GPI-Anchored)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Viral Envelope Proteins)
SB  - IM
MH  - Animals
MH  - Carrier Proteins/*metabolism
MH  - Cats
MH  - Cell Polarity
MH  - Cells, Cultured
MH  - Epithelial Cells/virology
MH  - Filoviridae/genetics/*metabolism
MH  - Folate Receptors, GPI-Anchored
MH  - *Genetic Vectors
MH  - Humans
MH  - Immunodeficiency Virus, Feline/genetics/metabolism/*pathogenicity
MH  - *Receptors, Cell Surface
MH  - Respiratory System/cytology/*virology
MH  - *Transduction, Genetic
MH  - Viral Envelope Proteins/genetics/*metabolism
PMC - PMC154009
EDAT- 2003/04/30 05:00
MHDA- 2003/06/05 05:00
PMCR- 2003/05/01
CRDT- 2003/04/30 05:00
PHST- 2003/04/30 05:00 [pubmed]
PHST- 2003/06/05 05:00 [medline]
PHST- 2003/04/30 05:00 [entrez]
PHST- 2003/05/01 00:00 [pmc-release]
AID - 2008 [pii]
AID - 10.1128/jvi.77.10.5902-5910.2003 [doi]
PST - ppublish
SO  - J Virol. 2003 May;77(10):5902-10. doi: 10.1128/jvi.77.10.5902-5910.2003.