title: A chimeric adenovirus vector encoding reovirus attachment protein sigma1 targets cells expressing junctional adhesion molecule 1.
abstract: The utility of adenovirus (Ad) vectors for gene transduction can be limited by receptor specificity. We developed a gene-delivery vehicle in which the potent Ad5 vector was genetically reengineered to display the mucosal-targeting sigma1 protein of reovirus type 3 Dearing (T3D). A sigma1 construct containing all but a small virion-anchoring domain was fused to the N-terminal 44 aa of Ad5 fiber. This chimeric attachment protein Fibtail-T3Dsigma1 forms trimers and assembles onto Ad virions. Fibtail-T3Dsigma1 was recombined into the Ad5 genome, replacing sequences encoding wild-type fiber. The resulting vector, Ad5-T3Dsigma1, expresses Fibtail-T3Dsigma1 and infects Chinese hamster ovary cells transfected with human or mouse homologs of the reovirus receptor, junctional adhesion molecule 1 (JAM1), but not the coxsackievirus and Ad receptor. Treatment of Caco-2 intestinal epithelial cells with either JAM1-specific antibody or neuraminidase reduced transduction by Ad5-T3Dsigma1, and their combined effect decreased transduction by 95%. Ad5-T3Dsigma1 transduces primary cultures of human dendritic cells substantially more efficiently than does Ad5, and this transduction depends on expression of JAM1. These data provide strong evidence that Ad5-T3Dsigma1 can be redirected to cells expressing JAM1 and sialic acid for application as a vaccine vector.
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX 77005, USA.
authors.forename: George T
authors.initials: GT
authors.lastname: Mercier
authors.forename: Jacquelyn A
authors.initials: JA
authors.lastname: Campbell
authors.forename: James D
authors.initials: JD
authors.lastname: Chappell
authors.forename: Thilo
authors.initials: T
authors.lastname: Stehle
authors.forename: Terence S
authors.initials: TS
authors.lastname: Dermody
authors.forename: Michael A
authors.initials: MA
authors.lastname: Barry
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D016466:CHO Cells; D018938:Caco-2 Cells; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D005822:Genetic Vectors; D006801:Humans; D062726:Junctional Adhesion Molecules; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics* / Q000378:metabolism; D012087:Reoviridae / Q000502:physiology*; D014162:Transfection
chemical_list: D015815:Cell Adhesion Molecules; D062726:Junctional Adhesion Molecules; D011991:Receptors, Virus; D019158:N-Acetylneuraminic Acid