A chimeric adenovirus vector encoding reovirus attachment protein σ1 targets cells expressing junctional adhesion molecule 1

George T. Mercier, Jacquelyn A. Campbell, James D. Chappell, Thilo Stehle, Terence S. Dermody, Michael A. Barry

Research output: Contribution to journalArticle

66 Scopus citations

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 σ1 protein of reovirus type 3 Dearing (T3D). A σ1 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-T3Dσ1 forms trimers and assembles onto Ad virions. Fibtail-T3Dσ1 was recombined into the Ad5 genome, replacing sequences encoding wild-type fiber. The resulting vector, Ad5-T3Dσ1, expresses Fibtail-T3Dσ1 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-T3Dσ1, and their combined effect decreased transduction by 95%. Ad5-T3Dσ1 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-T3Dσ1 can be redirected to cells expressing JAM1 and sialic acid for application as a vaccine vector.

Original languageEnglish (US)
Pages (from-to)6188-6193
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number16
DOIs
StatePublished - Apr 20 2004

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