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Human replication-deficient adenovirus (AdV) 5 is a promising vaccine vector for delivery of recombinant antigens. Although the mechanism of AdV attachment and penetration has been extensively studied in permissive cell lines, few studies have addressed the interaction of AdV with DC. In this study, we investigated the interaction of bovine skin-migrating DC and replication-deficient AdV-based vaccine vectors. We found that, despite lack of expression of Coxsackie B\u2013Adenovirus Receptor and other known adenovirus receptors, AdV readily enters skin-draining DC via an actin-dependent endocytosis. Virus exit from endosomes was pH independent, and neutralizing antibodies did not prevent virus entry but did prevent virus translocation to the nucleus. We also show that combining adenovirus with adjuvant increases the absolute number of intracellular virus particles per DC but not the number of DC containing intracellular virus. This results in increased trans-gene expression and antigen presentation. We propose that, in the absence of Coxsackie B\u2013Adenovirus Receptor and other known receptors, AdV5-based vectors enter skin-migrating DC using actin-dependent endocytosis which occurs in skin-migrating DC, and its relevance to vaccination strategies and vaccine vector targeting is discussed.<\/jats:p>","DOI":"10.1099\/jgv.0.000581","type":"journal-article","created":{"date-parts":[[2016,8,15]],"date-time":"2016-08-15T20:12:23Z","timestamp":1471291943000},"page":"2703-2718","source":"Crossref","is-referenced-by-count":4,"title":["Transduction of skin-migrating dendritic cells by human adenovirus 5 occurs via an actin-dependent phagocytic pathway"],"prefix":"10.1099","volume":"97","author":[{"given":"Efrain","family":"Guzman","sequence":"first","affiliation":[{"name":"The Pirbright Institute, Ash Road, Woking, Surrey GU240NF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geraldine","family":"Taylor","sequence":"additional","affiliation":[{"name":"The Pirbright 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