Universität zu Köln

Tsoukas, Raphael L., Volkwein, Wolfram, Gao, Jian, Schiwon, Maren, Bahlmann, Nora, Dittmar, Thomas ORCID: 0000-0001-8505-3424, Hagedorn, Claudia ORCID: 0000-0001-7010-4807, Ehrke-Schulz, Eric ORCID: 0000-0001-8154-9860, Zhang, Wenli, Baiker, Armin and Ehrhardt, Anja (2022). A Human In Vitro Model to Study Adenoviral Receptors and Virus Cell Interactions. Cells, 11 (5). BASEL: MDPI. ISSN 2073-4409

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Abstract

To develop adenoviral cell- or tissue-specific gene delivery, understanding of the infection mechanisms of adenoviruses is crucial. Several adenoviral attachment proteins such as CD46, CAR and sialic acid have been identified and studied. However, most receptor studies were performed on non-human cells. Combining our reporter gene-tagged adenovirus library with an in vitro human gene knockout model, we performed a systematic analysis of receptor usage comparing different adenoviruses side-by-side. The CRISPR/Cas9 system was used to knockout CD46 and CAR in the human lung epithelial carcinoma cell line A549. Knockout cells were infected with 22 luciferase-expressing adenoviruses derived from adenovirus species B, C, D and E. HAdV-B16, -B21 and -B50 from species B1 as well as HAdV-B34 and -B35 were found to be CD46-dependent. HAdV-C5 and HAdV-E4 from species E were found to be CAR-dependent. Regarding cell entry of HAdV-B3 and -B14 and all species D viruses, both CAR and CD46 play a role, and here, other receptors or attachment structures may also be important since transductions were reduced but not completely inhibited. The established human knockout cell model enables the identification of the most applicable adenovirus types for gene therapy and to further understand adenovirus infection biology.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tsoukas, Raphael L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Volkwein, Wolfram UNSPECIFIED UNSPECIFIED UNSPECIFIED Gao, Jian UNSPECIFIED UNSPECIFIED UNSPECIFIED Schiwon, Maren UNSPECIFIED UNSPECIFIED UNSPECIFIED Bahlmann, Nora UNSPECIFIED UNSPECIFIED UNSPECIFIED Dittmar, Thomas UNSPECIFIED orcid.org/0000-0001-8505-3424 UNSPECIFIED Hagedorn, Claudia UNSPECIFIED orcid.org/0000-0001-7010-4807 UNSPECIFIED Ehrke-Schulz, Eric UNSPECIFIED orcid.org/0000-0001-8154-9860 UNSPECIFIED Zhang, Wenli UNSPECIFIED UNSPECIFIED UNSPECIFIED Baiker, Armin UNSPECIFIED UNSPECIFIED UNSPECIFIED Ehrhardt, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-669447
DOI:	10.3390/cells11050841
Journal or Publication Title:	Cells
Volume:	11
Number:	5
Date:	2022
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2073-4409
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RESPIRATORY-INFECTIONS; DIARRHEAL FECES; SEROTYPES 3; CD46; IMMUNOCOMPETENT; COXSACKIEVIRUS; OUTBREAK; CHILDREN; BINDING; SAMPLES Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66944