Influence of Heparan Sulfate Proteoglycans and Factor X on species D Human Adenovirus Uptake and Transduction
More than 100 human adenovirus (Ad) types were identified, of which species D comprises the largest group. Heparan sulfate proteoglycans (HSPGs) were shown to function as cell surface receptors for cell binding and uptake of some Ads, but a systematic analysis of species D Ads is lacking. Previous r...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/15/1/55 |
| _version_ | 1827621325142753280 |
|---|---|
| author | Katrin Schröer Montaha Alshawabkeh Sebastian Schellhorn Katrin Bronder Wenli Zhang Anja Ehrhardt |
| author_facet | Katrin Schröer Montaha Alshawabkeh Sebastian Schellhorn Katrin Bronder Wenli Zhang Anja Ehrhardt |
| author_sort | Katrin Schröer |
| collection | DOAJ |
| description | More than 100 human adenovirus (Ad) types were identified, of which species D comprises the largest group. Heparan sulfate proteoglycans (HSPGs) were shown to function as cell surface receptors for cell binding and uptake of some Ads, but a systematic analysis of species D Ads is lacking. Previous research focused on Ad5 and blood coagulation factor X (FX) complexes, which revealed that Ad5 can transduce cells with low expression levels of its main coxsackievirus-adenovirus receptor in the presence of high HSPG expression levels in a FX dependent manner. Based on our reporter gene-tagged Ad-library, we explored for the first time a broad spectrum of species D Ads to study the role of HSPG on their cellular uptake. This study was performed on three Chinese Hamster Ovary (CHO) cell lines with different forms of HSPG (only proteoglycan (745), non-sulfated HSPG (606) or sulfated HSPG (K1)). The effect of Ad:FX complexes on Ad uptake was explored in the presence of physiological levels of FX in blood (6–10 µg/mL). We found that sulfation of HSPG plays an important role in cellular uptake and transduction of FX-bound Ad5 but neither HSPG nor FX influenced uptake of all tested species D Ads. Because FX has no influence on transduction efficiencies of species D Ads and therefore may not bind to them, these Ads may not be protected from attack by neutralizing IgM antibodies or the complement pathway, which may have implications for species D Ads used as vaccine and gene therapy vectors. |
| first_indexed | 2024-03-09T11:03:08Z |
| format | Article |
| id | doaj.art-3cd6889d1e644ad3b912105bfbc3b2e1 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T11:03:08Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-3cd6889d1e644ad3b912105bfbc3b2e12023-12-01T01:07:26ZengMDPI AGViruses1999-49152022-12-011515510.3390/v15010055Influence of Heparan Sulfate Proteoglycans and Factor X on species D Human Adenovirus Uptake and TransductionKatrin Schröer0Montaha Alshawabkeh1Sebastian Schellhorn2Katrin Bronder3Wenli Zhang4Anja Ehrhardt5Virology and Microbiology, Center for Biomedical Education and Research (ZBAF), Department of Human Medicine, Witten/Herdecke University, 58453 Witten, GermanyVirology and Microbiology, Center for Biomedical Education and Research (ZBAF), Department of Human Medicine, Witten/Herdecke University, 58453 Witten, GermanyVirology and Microbiology, Center for Biomedical Education and Research (ZBAF), Department of Human Medicine, Witten/Herdecke University, 58453 Witten, GermanyVirology and Microbiology, Center for Biomedical Education and Research (ZBAF), Department of Human Medicine, Witten/Herdecke University, 58453 Witten, GermanyVirology and Microbiology, Center for Biomedical Education and Research (ZBAF), Department of Human Medicine, Witten/Herdecke University, 58453 Witten, GermanyVirology and Microbiology, Center for Biomedical Education and Research (ZBAF), Department of Human Medicine, Witten/Herdecke University, 58453 Witten, GermanyMore than 100 human adenovirus (Ad) types were identified, of which species D comprises the largest group. Heparan sulfate proteoglycans (HSPGs) were shown to function as cell surface receptors for cell binding and uptake of some Ads, but a systematic analysis of species D Ads is lacking. Previous research focused on Ad5 and blood coagulation factor X (FX) complexes, which revealed that Ad5 can transduce cells with low expression levels of its main coxsackievirus-adenovirus receptor in the presence of high HSPG expression levels in a FX dependent manner. Based on our reporter gene-tagged Ad-library, we explored for the first time a broad spectrum of species D Ads to study the role of HSPG on their cellular uptake. This study was performed on three Chinese Hamster Ovary (CHO) cell lines with different forms of HSPG (only proteoglycan (745), non-sulfated HSPG (606) or sulfated HSPG (K1)). The effect of Ad:FX complexes on Ad uptake was explored in the presence of physiological levels of FX in blood (6–10 µg/mL). We found that sulfation of HSPG plays an important role in cellular uptake and transduction of FX-bound Ad5 but neither HSPG nor FX influenced uptake of all tested species D Ads. Because FX has no influence on transduction efficiencies of species D Ads and therefore may not bind to them, these Ads may not be protected from attack by neutralizing IgM antibodies or the complement pathway, which may have implications for species D Ads used as vaccine and gene therapy vectors.https://www.mdpi.com/1999-4915/15/1/55Human Adenovirus Species DChinese Hamster Ovarian Cell Linesheparan sulfate proteoglycanhuman blood-coagulation sactor X |
| spellingShingle | Katrin Schröer Montaha Alshawabkeh Sebastian Schellhorn Katrin Bronder Wenli Zhang Anja Ehrhardt Influence of Heparan Sulfate Proteoglycans and Factor X on species D Human Adenovirus Uptake and Transduction Viruses Human Adenovirus Species D Chinese Hamster Ovarian Cell Lines heparan sulfate proteoglycan human blood-coagulation sactor X |
| title | Influence of Heparan Sulfate Proteoglycans and Factor X on species D Human Adenovirus Uptake and Transduction |
| title_full | Influence of Heparan Sulfate Proteoglycans and Factor X on species D Human Adenovirus Uptake and Transduction |
| title_fullStr | Influence of Heparan Sulfate Proteoglycans and Factor X on species D Human Adenovirus Uptake and Transduction |
| title_full_unstemmed | Influence of Heparan Sulfate Proteoglycans and Factor X on species D Human Adenovirus Uptake and Transduction |
| title_short | Influence of Heparan Sulfate Proteoglycans and Factor X on species D Human Adenovirus Uptake and Transduction |
| title_sort | influence of heparan sulfate proteoglycans and factor x on species d human adenovirus uptake and transduction |
| topic | Human Adenovirus Species D Chinese Hamster Ovarian Cell Lines heparan sulfate proteoglycan human blood-coagulation sactor X |
| url | https://www.mdpi.com/1999-4915/15/1/55 |
| work_keys_str_mv | AT katrinschroer influenceofheparansulfateproteoglycansandfactorxonspeciesdhumanadenovirusuptakeandtransduction AT montahaalshawabkeh influenceofheparansulfateproteoglycansandfactorxonspeciesdhumanadenovirusuptakeandtransduction AT sebastianschellhorn influenceofheparansulfateproteoglycansandfactorxonspeciesdhumanadenovirusuptakeandtransduction AT katrinbronder influenceofheparansulfateproteoglycansandfactorxonspeciesdhumanadenovirusuptakeandtransduction AT wenlizhang influenceofheparansulfateproteoglycansandfactorxonspeciesdhumanadenovirusuptakeandtransduction AT anjaehrhardt influenceofheparansulfateproteoglycansandfactorxonspeciesdhumanadenovirusuptakeandtransduction |