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Binding of adenoviral fiber knob to the coxsackievirus-adenovirus receptor is crucial for transduction of fetal muscle.
Hum Gene Ther. 2003 May 01; 14(7):645-9.HG

Abstract

Adenoviral (Ad) infection involves attachment mediated by the Ad fiber protein binding to the coxsackievirus-adenovirus receptor (CAR) of a target cell and internalization facilitated by the interaction of the Ad penton base protein with alpha(v) integrins. To understand the relative importance of the Ad binding and internalization steps for the transduction of fetal skeletal muscle, we used a panel of genetically modified vectors that specifically ablate the fiber-CAR interaction (AdL.F*), the penton base-alpha(v) integrin interaction (AdL.PB*), or both (AdL.PB*F*) to transduce embryonic day 16 (E-16) mouse muscle in vivo and primary E-16 muscle cells in vitro. Quantification of transgene expression and vector genome copies revealed a striking absence of E-16 muscle transduction by AdL.F* and AdL.PB*F*. In contrast, fetal muscle transduction with AdL.PB* was not significantly different than with the unmodified vector. Similar results were observed with in vitro Ad infection studies in primary E-16 muscle cells. From these data we conclude that the fiber-CAR interaction is important for the transduction of fetal muscle by Ad vectors. The high dependence on fiber-CAR binding will impact the development of strategies for Ad vector retargeting to achieve muscle-specific transduction in utero.

Authors+Show Affiliations

Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12804146

Citation

Bilbao, Roberto, et al. "Binding of Adenoviral Fiber Knob to the Coxsackievirus-adenovirus Receptor Is Crucial for Transduction of Fetal Muscle." Human Gene Therapy, vol. 14, no. 7, 2003, pp. 645-9.
Bilbao R, Srinivasan S, Reay D, et al. Binding of adenoviral fiber knob to the coxsackievirus-adenovirus receptor is crucial for transduction of fetal muscle. Hum Gene Ther. 2003;14(7):645-9.
Bilbao, R., Srinivasan, S., Reay, D., Goldberg, L., Hughes, T., Roelvink, P. W., Einfeld, D. A., Wickham, T. J., & Clemens, P. R. (2003). Binding of adenoviral fiber knob to the coxsackievirus-adenovirus receptor is crucial for transduction of fetal muscle. Human Gene Therapy, 14(7), 645-9.
Bilbao R, et al. Binding of Adenoviral Fiber Knob to the Coxsackievirus-adenovirus Receptor Is Crucial for Transduction of Fetal Muscle. Hum Gene Ther. 2003 May 1;14(7):645-9. PubMed PMID: 12804146.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Binding of adenoviral fiber knob to the coxsackievirus-adenovirus receptor is crucial for transduction of fetal muscle. AU - Bilbao,Roberto, AU - Srinivasan,Suchitra, AU - Reay,Daniel, AU - Goldberg,Laura, AU - Hughes,Tiffany, AU - Roelvink,Peter W, AU - Einfeld,David A, AU - Wickham,Thomas J, AU - Clemens,Paula R, PY - 2003/6/14/pubmed PY - 2003/10/3/medline PY - 2003/6/14/entrez SP - 645 EP - 9 JF - Human gene therapy JO - Hum Gene Ther VL - 14 IS - 7 N2 - Adenoviral (Ad) infection involves attachment mediated by the Ad fiber protein binding to the coxsackievirus-adenovirus receptor (CAR) of a target cell and internalization facilitated by the interaction of the Ad penton base protein with alpha(v) integrins. To understand the relative importance of the Ad binding and internalization steps for the transduction of fetal skeletal muscle, we used a panel of genetically modified vectors that specifically ablate the fiber-CAR interaction (AdL.F*), the penton base-alpha(v) integrin interaction (AdL.PB*), or both (AdL.PB*F*) to transduce embryonic day 16 (E-16) mouse muscle in vivo and primary E-16 muscle cells in vitro. Quantification of transgene expression and vector genome copies revealed a striking absence of E-16 muscle transduction by AdL.F* and AdL.PB*F*. In contrast, fetal muscle transduction with AdL.PB* was not significantly different than with the unmodified vector. Similar results were observed with in vitro Ad infection studies in primary E-16 muscle cells. From these data we conclude that the fiber-CAR interaction is important for the transduction of fetal muscle by Ad vectors. The high dependence on fiber-CAR binding will impact the development of strategies for Ad vector retargeting to achieve muscle-specific transduction in utero. SN - 1043-0342 UR - https://www.unboundmedicine.com/medline/citation/12804146/Binding_of_adenoviral_fiber_knob_to_the_coxsackievirus_adenovirus_receptor_is_crucial_for_transduction_of_fetal_muscle_ L2 - https://www.liebertpub.com/doi/10.1089/104303403321618155?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -