Human adenovirus type 17 from species D transduces endothelial cells and human CD46 is involved in cell entry

  • More than 70 human adenoviruses with type-dependent pathogenicity have been identified but biological information about the majority of these virus types is scarce. Here we employed multiple sequence alignments and structural information to predict receptor usage for the development of an adenoviral vector with novel biological features. We report the generation of a cloned adenovirus based on human adenovirus type 17 (HAdV17) with high sequence homology to the well characterized human adenovirus type 37 (HAdV37) that causes epidemic keratoconjunctivitis (EKC). Our study revealed that human CD46 (CD46) is involved in cell entry of HAdV17. Moreover, we found that HAdV17 infects endothelial cells (EC) in vitro including primary cells at higher efficiencies compared to the commonly used human adenovirus type 5 (HAdV5). Using a human CD46 transgenic mouse model, we observed that HAdV17 displays a broad tropism in vivo after systemic injection and that it transduces ECs in this mouse model. We conclude that the HAdV17-based vector may provide a novel platform for gene therapy.

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Author:Jing Liu, Philip Patrick Boehme, Wenli Zhang, Jun Fu, Roma Yumul, Kemal Mese, Raphael Tsoukas, Manish Solanki, Michael Kaufmann, Ruirui Lu, Achim SchmidtkoORCiDGND, A. Francis Stewart, André Lieber, Anja Ehrhardt
URN:urn:nbn:de:hebis:30:3-471787
DOI:https://doi.org/10.1038/s41598-018-31713-x
ISSN:2045-2322
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/30194327
Parent Title (English):Scientific reports
Publisher:Macmillan Publishers Limited, part of Springer Nature
Place of publication:[London]
Document Type:Article
Language:English
Year of Completion:2018
Date of first Publication:2018/09/07
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/09/11
Tag:Genetic transduction; Molecular medicine
Volume:8
Issue:1, Art. 13442
Page Number:14
First Page:1
Last Page:14
Note:
Rights and permissions: Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
HeBIS-PPN:437751279
Institutes:Biochemie, Chemie und Pharmazie / Pharmazie
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0