Coxsackie adenovirus receptor and ανβ3/ανβ5 integrins in adenovirus gene transfer of rat cochlea

Venail, F.; Wang, J; Ruel, Jérôme; Ballana, Ester; Rebillard, Guy; Eybalin, Michel; Arbonés, Mariona; Bosch, Assumpció; Puel, Jean–Luc

doi:10.1038/sj.gt.3302826

Cited by 35 publications

(31 citation statements)

References 30 publications

(24 reference statements)

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“…37,38 Our demonstration of adenoviral transfection in human sensory epithelia suggests CAR receptors are present in the mature human inner ear and supports the development of adenovirus, or other vectors that bind the CAR receptor, for future human application.…”

Section: Cell Viability and Availabilitymentioning

confidence: 54%

An in vitro model system to study gene therapy in the human inner ear

et al. 2007

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The confined fluid-filled labyrinth of the human inner ear presents an opportunity for introduction of gene therapy reagents designed to treat hearing and balance dysfunction. Here we present a novel model system derived from the sensory epithelia of human vestibular organs and show that the tissue can survive up to 5 days in vitro. We generated organotypic cultures from 26 human sensory epithelia excised at the time of labyrinthectomy for intractable Meniere's disease or vestibular schwannoma. We applied multiply deleted adenoviral vectors at titers between 10 5 and 10 8 viral particles/ml directly to the cultures for 4-24 h and examined the tissue 12-96 h post-transfection. We noted robust expression of the exogenous transgene, green fluorescent protein (GFP), in hair cells and supporting cells suggesting both were targets of adenoviral transfection. We also transfected cultures with a vector that carried the genes for GFP and KCNQ4, a potassium channel subunit that causes dominant-progressive hearing loss when mutated. We noted a positive correlation between GFP fluorescence and KCNQ4 immunolocalization. We conclude that our in vitro model system presents a novel and effective experimental paradigm for evaluation of gene therapy reagents designed to restore cellular function in patients who suffer from inner ear disorders.

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Section: Cell Viability and Availabilitymentioning

confidence: 54%

An in vitro model system to study gene therapy in the human inner ear

et al. 2007

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“…CAR is present in cells of the auditory epithelium but its distribution does not completely explain the pattern of cellular transduction in this epithelium, during development and in the mature tissue [28, 29]. Lack of transgene expression in hair cells is especially intriguing, considering the presence of CAR in these cells.…”

Section: Characteristics Of Adenoviral Gene Transduction In the Innermentioning

confidence: 99%

Gene Therapy in the Inner Ear Using Adenovirus Vectors

Husseman

Raphael

2009

Gene Therapy of Cochlear Deafness

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Therapies for the protection and regeneration of auditory hair cells are of great interest given the significant monetary and lifestyle impact of hearing loss. The past decade has seen tremendous advances in the use of adenoviral vectors to achieve these aims. Preliminary data demonstrated the functional capacity of this technique as adenoviral-induced expression of neurotrophic and growth factors protected hair cells and spiral ganglion neurons from ototoxic insults. Subsequent efforts confirmed the feasibility of adenoviral transfection of cells in the auditory neuroepithelium via cochleostomy into the scala media. Most recently, efforts have focused on regeneration of depleted hair cells. Mammalian hearing loss is generally considered a permanent insult as the auditory epithelium lacks a basal layer capable of producing new hair cells. Recently, the transcription factor Atoh1 has been found to play a critical role in hair cell differentiation. Adenoviral-mediated overexpression of Atoh1 in culture and in vivo have shown the ability to regenerate auditory and vestibular hair cells by causing transdifferentiation of neighboring epithelial-supporting cells. Functional recovery of both the auditory and vestibular systems has been documented following adenoviral induced Atoh1 overexpression.

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“…Anatomical barriers are present that alter CAR's accessibility to adenovirus. Adenoviruses do not pass through the perilymph-endolymph barrier, as has previously been shown in guinea pigs [35] . After attaching the host cells by binding to CAR, adenovirus is internalized through integrins ␣ ␤ 3 or ␣ ␤ 5 [38,39] .…”

Section: Receptors and Affinity To The Inner Earmentioning

confidence: 67%

“…Both of them are essential for adenovirus infection. Venail et al [35] reported that antibody against integrins-␣ did not abolish or even had no influence on adenovirus infection. There, results can only be explained by a noneffective blockage of integrin pathway.…”

Section: Receptors and Affinity To The Inner Earmentioning

confidence: 99%

“…Interestingly, although most cell types stained positive for CAR, only a small subpopulation of these cells can be infected by adenovirus. In vivo, one study showed that the most efficient transduction is seen in mesothelial cells lining the perilymphatic fluids, whereas the sensory hair cells of the organ of Corti and the spiral ganglion neurons were not transduced [35] . In histological preparations, staining for CAR was detected in stria vascularis, Reissner's membrane and the spiral ligament in patterns that correlate well with adenovirus infection of adult cochleae [36,37] .…”

Section: Receptors and Affinity To The Inner Earmentioning

confidence: 99%

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Do Viruses Cause Inner Ear Disturbances?

Pyykkö

Zou

2008

ORL

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The association of viral infection to inner ear disease is controversial. Experiments on animals show that several viruses are capable of causing hearing loss, if applied into the perilymph. Some of these have specific affinity to the cellular type of the inner ear, as sensory epithelia and cochlear nerve. Some viruses as adenoviruses and Coxsackie virus B have specific CAR receptors that are identified in different cell types, whereas other act by attaching onto nonspecific cellular surface receptors. Some viruses such as varicella zoster virus (VZV) do not cause disease in rodents. We assessed 273 patients with clinical, serological, neuro-otologic and endoscopic evaluations. Of the 273 patients, 43 served as control subjects. The patients either had Ménière’s disease (n = 158), recurrent vertigo of unknown etiology (n = 56), or hearing loss (n = 17). Antibodies against neurotropic and common viruses were evaluated. VZV, influenza B, CBV5 and RSV titers were significantly elevated in patients with inner ear disease when compared with the control group. In analyzing the internal relationship, VZV and influenza B were intercorrelated. We did not find a correlation between hearing loss and viral titers. In conclusion, VZV, Coxsackie virus B5 and influenza B virus may be the main causes of inner ear disorder. The spiral and Scarpa’s ganglion are potential sites harboring viral DNA for possible latent infection.

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Coxsackie adenovirus receptor and ανβ3/ανβ5 integrins in adenovirus gene transfer of rat cochlea

Cited by 35 publications

References 30 publications

An in vitro model system to study gene therapy in the human inner ear

An in vitro model system to study gene therapy in the human inner ear

Gene Therapy in the Inner Ear Using Adenovirus Vectors

Do Viruses Cause Inner Ear Disturbances?

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