PhD ceremony Ms. T.E. Hoornweg: 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 is spreading rapidly around the world; already millions of people are 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 is able to successfully enter and infect its host cell. With fluorescent labeled virus we were able to visualize the transport of the virus into the cell in real-time. Furthermore, we identified which host cell proteins the virus needs to infect in its target cell. One of our most important findings is 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 is 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.

Dissertation: http://hdl.handle.net/11370/31cfcb0d-d415-455a-b86d-b99ed89653dc