Abstract
Breaking Barriers – early events in chikungunya and dengue virus infections
Chikungunya and dengue are two mosquito-borne diseases which are mainly transmitted in the (sub)tropical parts of the world. Since 2006 chikungunya spread rapidly around the world; already millions of people were infected with this debilitating disease. Dengue is at present the most common mosquito-borne viral disease in the world. Although dengue infections are usually mild, they can progress into severe disease, which can be fatal if left untreated.
At the start of this thesis little was known about chikungunya virus infections. Therefore, we looked into the mechanism via which chikungunya virus was able to successfully enter and infect its host cell. By labelling the virus fluorescently, we were able to visualize the transport of the virus into the cell in real-time. Furthermore, we discovered which host cell proteins the virus needs to infect its target cell. One of our most important findings was that an intact cellular skeleton is very important for the release of the chikungunya genome.
Antibodies play an important role in the development of severe dengue disease. Under certain conditions, antibodies enhance the number of infected cells and increase the number of viruses produced per cell. However, the mechanism behind these observations was still under debate. In this thesis, we show that dengue fuses more readily with its host cell in the presence of antibodies. However, the increase in fusion potential does not trigger an antiviral response. Consequently, the incoming genomes are efficiently replicated inside the cell, and more viral particles are produced.
Chikungunya and dengue are two mosquito-borne diseases which are mainly transmitted in the (sub)tropical parts of the world. Since 2006 chikungunya spread rapidly around the world; already millions of people were infected with this debilitating disease. Dengue is at present the most common mosquito-borne viral disease in the world. Although dengue infections are usually mild, they can progress into severe disease, which can be fatal if left untreated.
At the start of this thesis little was known about chikungunya virus infections. Therefore, we looked into the mechanism via which chikungunya virus was able to successfully enter and infect its host cell. By labelling the virus fluorescently, we were able to visualize the transport of the virus into the cell in real-time. Furthermore, we discovered which host cell proteins the virus needs to infect its target cell. One of our most important findings was that an intact cellular skeleton is very important for the release of the chikungunya genome.
Antibodies play an important role in the development of severe dengue disease. Under certain conditions, antibodies enhance the number of infected cells and increase the number of viruses produced per cell. However, the mechanism behind these observations was still under debate. In this thesis, we show that dengue fuses more readily with its host cell in the presence of antibodies. However, the increase in fusion potential does not trigger an antiviral response. Consequently, the incoming genomes are efficiently replicated inside the cell, and more viral particles are produced.
| Original language | English |
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| Qualification | Doctor of Philosophy |
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| Award date | 16-Nov-2016 |
| Place of Publication | [Groningen] |
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| Print ISBNs | 978-90-367-9245-5 |
| Electronic ISBNs | 978-90-367-9244-8 |
| Publication status | Published - 2016 |