Role of Coxsackie- and adenovirus receptor (CAR) genetic variants, CAR- and adenovirus-based synthetic peptides, and CAR-shedding in CAR-mediated virus entry

Herrmann L (2021)
Bielefeld: Universität Bielefeld.

Bielefelder E-Dissertation | Englisch
 
Download
OA 7.02 MB
Autor*in
Herrmann, Leonie
Abstract / Bemerkung
The Coxsackie- and adenovirus receptor (CAR) is a transmembrane cell adhesion molecule with two extracellular immunoglobulin domains. It is located at cell-cell contacts, for example at intercalated discs between cardiomyocytes or at tight junctions in lung and intestines. CAR forms homodimers with its membrane-distal immunoglobulin domain D1 and is involved in cell adhesion, proliferation, and migration. It acts as a pathfinder protein during embryogenesis and during tissue remodelling after injuries. Next to its physiological functions, CAR aroused interest due to its role in cell entry and attachment of Coxsackie- and adenoviruses. Both viruses use CAR D1 as binding site and are a major cause for viral-induced myocarditis.
I investigated three different mechanisms that might influence CAR´s interaction with viruses. First, five genetic variants in the CAR-coding gene that are most frequent in human population were analysed regarding their influence on cell adhesion and proliferation as well as on virus internalisation. No differences were observed among the variants compared to wild type CAR. This gives further evidence to the idea of CAR as an indispensable protein during embryogenesis, for which until now no pathogenic genetic variant has been described.
Second, I designed peptides to use them as virus entry inhibitors. Synthetic peptides that inhibit virus-receptor interactions have not been described for adenoviruses yet. In this work, peptides based on known interaction motifs either of CAR D1 or of adenovirus binding knob were used. No peptide inhibited adenovector cell entry significantly. Probably, peptide binding was too weak to compete with virus-CAR interaction.
Third, several soluble proteases that are secreted by immune cells during myocarditis were tested for their ability to shed CAR, i.e. to release its extracellular domain through proteolysis. Soluble CAR extracellular domain could function as a virus trap and inhibit ongoing viral infections. I used human soluble or membranous CAR expressed by *E. coli* or mammalian cells to screen for potential ectodomain sheddases. For neutrophil elastase, both incubation time and protease concentration comply with a physiologically relevant process. CAR cleavage products comprise complete D1 domain, which could make them biologically active virus traps. Thus, CAR-shedding through neutrophil elastase, which is described here for the first time, might be a host defense mechanism against Coxsackie- and adenoviruses.
Jahr
2021
Page URI
https://pub.uni-bielefeld.de/record/2951592

Zitieren

Herrmann L. Role of Coxsackie- and adenovirus receptor (CAR) genetic variants, CAR- and adenovirus-based synthetic peptides, and CAR-shedding in CAR-mediated virus entry. Bielefeld: Universität Bielefeld; 2021.
Herrmann, L. (2021). Role of Coxsackie- and adenovirus receptor (CAR) genetic variants, CAR- and adenovirus-based synthetic peptides, and CAR-shedding in CAR-mediated virus entry. Bielefeld: Universität Bielefeld. https://doi.org/10.4119/unibi/2951592
Herrmann, L. (2021). Role of Coxsackie- and adenovirus receptor (CAR) genetic variants, CAR- and adenovirus-based synthetic peptides, and CAR-shedding in CAR-mediated virus entry. Bielefeld: Universität Bielefeld.
Herrmann, L., 2021. Role of Coxsackie- and adenovirus receptor (CAR) genetic variants, CAR- and adenovirus-based synthetic peptides, and CAR-shedding in CAR-mediated virus entry, Bielefeld: Universität Bielefeld.
L. Herrmann, Role of Coxsackie- and adenovirus receptor (CAR) genetic variants, CAR- and adenovirus-based synthetic peptides, and CAR-shedding in CAR-mediated virus entry, Bielefeld: Universität Bielefeld, 2021.
Herrmann, L.: Role of Coxsackie- and adenovirus receptor (CAR) genetic variants, CAR- and adenovirus-based synthetic peptides, and CAR-shedding in CAR-mediated virus entry. Universität Bielefeld, Bielefeld (2021).
Herrmann, Leonie. Role of Coxsackie- and adenovirus receptor (CAR) genetic variants, CAR- and adenovirus-based synthetic peptides, and CAR-shedding in CAR-mediated virus entry. Bielefeld: Universität Bielefeld, 2021.
Alle Dateien verfügbar unter der/den folgenden Lizenz(en):
Creative Commons Namensnennung 4.0 International Public License (CC-BY 4.0):
Volltext(e)
Access Level
OA Open Access
Zuletzt Hochgeladen
2021-02-23T13:35:59Z
MD5 Prüfsumme
e9721b84f481357c93093e627a8e2f8a

Export

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Suchen in

Google Scholar