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Titolo:
Apical localization of the coxsackie-adenovirus receptor by glycosyl-phosphatidylinositol modification is sufficient for adenovirus-mediated gene transfer through the apical surface of human airway epithelia
Autore:
Walters, RW; vant Hof, W; Yi, SMP; Schroth, MK; Zabner, J; Crystal, RG; Welsh, MJ;
Indirizzi:
Univ Iowa, Coll Med, Howard Hughes Med Inst, Iowa City, IA 52242 USA Univ Iowa Iowa City IA USA 52242 Hughes Med Inst, Iowa City, IA 52242 USA Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA Univ IowaIowa City IA USA 52242 pt Internal Med, Iowa City, IA 52242 USA Univ Iowa, Coll Med, Dept Physiol & Biophys, Iowa City, IA 52242 USA Univ Iowa Iowa City IA USA 52242 ysiol & Biophys, Iowa City, IA 52242 USA Univ Iowa, Coll Med, Dept Otolaryngol, Iowa City, IA 52242 USA Univ Iowa Iowa City IA USA 52242 ept Otolaryngol, Iowa City, IA 52242 USA Cornell Univ, Div Pulm & Crit Care Med, New York, NY 10021 USA Cornell Univ New York NY USA 10021 Crit Care Med, New York, NY 10021 USA Cornell Univ, Weill Med Coll, Inst Med Genet, New York, NY 10021 USA Cornell Univ New York NY USA 10021 Inst Med Genet, New York, NY 10021 USA Univ Wisconsin, Sch Med, Dept Pediat, Madison, WI 53792 USA Univ Wisconsin Madison WI USA 53792 d, Dept Pediat, Madison, WI 53792 USA
Titolo Testata:
JOURNAL OF VIROLOGY
fascicolo: 16, volume: 75, anno: 2001,
pagine: 7703 - 7711
SICI:
0022-538X(200108)75:16<7703:ALOTCR>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
GPI-ANCHORED PROTEINS; TRANSMEMBRANE CONDUCTANCE REGULATOR; ALPHA-V INTEGRINS; CYSTIC-FIBROSIS; IN-VITRO; NASAL EPITHELIUM; TRANSFER VECTORS; CELLS; INFECTION; VIVO;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Welsh, MJ Univ Iowa, Coll Med, Howard Hughes Med Inst, 500 EMRB, Iowa City, IA 52242USA Univ Iowa 500 EMRB Iowa City IA USA 52242 Iowa City, IA 52242USA
Citazione:
R.W. Walters et al., "Apical localization of the coxsackie-adenovirus receptor by glycosyl-phosphatidylinositol modification is sufficient for adenovirus-mediated gene transfer through the apical surface of human airway epithelia", J VIROLOGY, 75(16), 2001, pp. 7703-7711

Abstract

In well-differentiated human airway epithelia, the coxsackie B and adenovirus type 2 and 5 receptor (CAR) resides primarily on the basolateral membrane. This location may explain the observation that gene transfer is inefficient when adenovirus vectors are applied to the apical surface. To further test this hypothesis and to investigate requirements and barriers to apicalgene transfer to differentiated human airway epithelia, we expressed CAR in which the transmembrane and cytoplasmic tail were replaced by a glycosyl-phosphatidylinositol (GPI) anchor (GPI-CAR). As controls, we expressed wild-type CAR and CAR lacking the cytoplasmic domain (Tailless-CAR). All three constructs enhanced gene transfer with similar efficiencies in fibroblasts. In airway epithelia, GPI-CAR localized specifically to the apical membrane, where it bound adenovirus and enhanced gene transfer to levels obtained when vector was applied to the basolateral membrane. Moreover, GPI-CAR facilitated gene transfer of the cystic fibrosis transmembrane conductance regulator to cystic fibrosis airway epithelia, correcting the Cl- transport defect. In contrast, when we expressed wild-type CAR it localized to the basolateral membrane and failed to increase apical gene transfer. Only a small amount of Tailless-CAR resided in the apical membrane, and the effects on apical virus binding and gene transfer were minimal. These data indicate that binding of adenovirus to an apical membrane receptor is sufficient to mediate effective gene transfer to human airway epithelia and that the cytoplasmic domain of CAR is not required for this process. The results suggest thattargeting apical receptors in differentiated airway epithelia may be sufficient for gene transfer in the genetic disease cystic fibrosis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 14:39:52