RESUMEN
Non-human adenoviruses such as bovine adenovirus type 3 (BAV-3) that do not replicate in human cells but can infect human cells in culture could provide an attractive alternative to human adenoviral vectors for gene therapy. In addition, a large-animal model for genetic diseases can be very useful for the assessment of the efficacy of adenovector-mediated gene delivery in man. Recombinant human subgroup C adenovectors use the coxsackie and adenovirus receptor (CAR) to enter their target cells. Through RT-PCR and sequencing we determined the complete coding sequence of bovine CAR which serves as the primary adenoviral attachment site on bovine cells. A multiple sequence alignment, involving all the previously identified CAR species (man, mouse, rat, pig, and dog) showed that bovine CAR was most related to porcine CAR (92% nucleotide similarity) and demonstrated a highly conserved adenovirus binding Ig1 domain.
Asunto(s)
Receptores Virales/química , Receptores Virales/genética , Secuencia de Aminoácidos , Animales , Bovinos , Clonación Molecular , Secuencia Conservada , Proteína de la Membrana Similar al Receptor de Coxsackie y Adenovirus , ADN Complementario/genética , Terapia Genética/veterinaria , Humanos , Mastadenovirus/genética , Mastadenovirus/metabolismo , Datos de Secuencia Molecular , Estructura Terciaria de Proteína , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Virales/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Alineación de Secuencia , Homología de SecuenciaRESUMEN
The human cellular receptor for group B coxsackieviruses and adenoviruses (HCAR) is a transmembrane glycoprotein which belongs to the immunoglobulin superfamily. We describe alternative splicing of the HCAR-gene and the existence of three exon-skipping splice variants in addition to the originally identified seven exon-encompassing mRNA transcript. Expression of the splice variants theoretically results in truncated proteins, possibly leading to impaired viral binding and/or the occurrence of soluble viral receptors due to the absence of the transmembranous region. Consequently, this could markedly influence the efficacy of an adenovirus subgroup C-mediated gene therapy.