Characterization of the expression of key adenoviral receptors CAR and integrin β₃/β₅ subunits on the membrane of human NT2 neurons

Authors: Huang, Deqi¹; Desbois, Angele²; Chen, Gao¹; Fang, Hung²; Hou, Sheng³

Source: Journal of Molecular Neuroscience, Volume 24, Number 2, June 2004 , pp. 323-328(6)

Buy & download fulltext article:

Price: $42.00 plus tax (Refund Policy)

Abstract:

Expression of therapeutic gene products in differentiated human NT2 neurons (NT2/Ns) is being explored for ex vivo gene therapy of human neurological diseases. In this study we determined the efficiency of adenovirus (Ad)-mediated gene delivery into NT2/Ns and characterized the expression of several key receptors known to be required for efficient Ad-mediated gene delivery. Undifferentiated NT2 cells and NT2/Ns were infected by Ad expressing green fluorescent protein at an efficiency of 33% and 17%, respectively—percentages much lower than the 92% infectivity obtained from a human non-neuronal cell line A549 cells. This relatively low infectivity of NT2/Ns might be caused by the extremely low expression of integrin subunit β₃ and the reduced expression of β₅ during differentiation. The expression of coxsackie-Ad receptor (CAR) was relatively high and remained constant during differentiation. Blocking CAR receptor using an antibody specific against CAR reduced Ad infectivity in a dose-dependent manner. These observations suggest that modulating the expression of integrin subunits β_3/5 or the functional heterodimer α_vβ_3/5 in human NT2/Ns may enhance adenoviral infectivity of NT2/Ns.

Keywords: Cosackie-adenovirus receptor; integrin αvβ3/5; NT2 neurons; replication-defective adenovirus

Document Type: Research article

DOI: http://dx.doi.org/10.1385/JMN:24:2:323

Affiliations: 1: Experimental Stroke Group, NRC Institute for Biological Sciences, National Research Council of Canada, K1A 0R6, Ottawa, Ontario, Canada, 2: Neurogenesis and Brain Repair Group, NRC Institute for Biological Sciences, National Research Council of Canada, K1A 0R6, Ottawa, Ontario, Canada, 3: Experimental Stroke Group, NRC Institute for Biological Sciences, National Research Council of Canada, K1A 0R6, Ottawa, Ontario, Canada, Email: sheng.hou@nrc.ca

Publication date: 2004-06-01