Virus:host interactions during chikungunya virus infection: Analyzing host cell factors and antiviral strategies

In the past decades we have witnessed a drastic re-emergence of mosquito-borne viruses. While millions of people are at risk to become infected there are no antiviral therapies or vaccines available to treat or prevent infection by these viruses. One of the rapidly spreading mosquito-borne viruses is chikungunya virus. Infection with chikungunya virus can lead to a debilitating illness including flu-like symptoms, headache, and long-lasting rheumatic disease symptoms. To develop antiviral therapies, it is a prerequisite to understand the virus:host interactions that lead to disease. In this thesis we investigated the virus:host interactions required for chikungunya virus replication. Emphasis was on identifying new cellular factors that are important for chikungunya virus infection and to explore whether these might serve as targets for antiviral therapeutics. We analyzed the role of the cellular receptor Mxra8 and microtubules in the early events of chikungunya virus infection. Moreover, we studied the antiviral activity of serotonergic drugs, heat shock protein inhibitors and the neutralizing antibody CHK-152. Overall, these research activities provide future perspectives on the cellular factors required for chikungunya virus infection that could be targeted for anti-chikungunya virus drug development.