1. ¹INSERM UMR 583, Physiopathologie et Thérapie des Déficits Sensoriels et Moteurs, Montpellier, France
2. ²Faculty of Medicine, Université Montpellier 1, Montpellier, France
3. ³Genes and Disease Program, Centre de Regulació Genómica-CRG-UPF, Barcelona, Spain
4. ⁴Department of Biochemistry and Molecular Biology, Centre of Animal Biotechnology and Gene Therapy (CBATEG) and Universitat Autonòma de Barcelona, Barcelona, Spain

Correspondence: Professor J-L Puel, Physiopathologie et Thérapie des Déficits Sensoriels et Moteurs, INSERM 583-INM, Inserum U583 and University of Montpellier 1, Hospital Saint Eloi, 80 avenue Augustin Fliche, Montpellier 34295, France. E-mail: puel@montp.inserm.fr

⁵These authors contributed equally to this work.

Received 18 January 2006; Revised 11 June 2006; Accepted 13 June 2006; Published online 3 August 2006.

Abstract

This study was designed to determine whether Coxsackie adenovirus receptor (CAR) and 3/5 integrin co-receptors are involved in adenovirus gene transfer in the rat cochlea. We find that CAR and integrin co-receptors are expressed in every cell subtype transduced by the adenoviral vector Ad5 E1–E3/cytomegalovirus/green fluorescent protein (GFP) on cochlear slices in vitro. The spiral ganglion neurons, which do not express CAR, were not transduced by the virus. Blocking these receptors by monoclonal antibodies decreased transgene expression, whereas disrupting tight junctions with ethylenediaminetetraacetic acid led to an increased transgene expression. However, sensory hair cells and strial cells also expressing CAR and integrins were not transduced by the vector. GFP expression was also studied in vivo. Perilymphatic perfusion of adenovirus in vivo did not affect hearing and only cells lining the perilymphatic spaces were transduced. Endolymphatic perfusion resulted in low-frequency hearing loss and although some cells of the organ of Corti were efficiently transduced, the sensory and the strial cells were not. Transduced sensory and strial cells were occasionally observed in cochleas after single shot of adenovirus. Pretreatment with anti-CAR and anti- antibodies decreases GFP expression in vivo, suggesting that the CAR/ integrin pathway is involved in adenovirus transduction in the cochlea.