PhD ceremony Ms. M.K.S. van Duijl-Richter: Dengue and Chikungunya Virus. Cell entry mechanisms and the impact of antibodies on infectivity

Dengue virus (DENV) and Chikungunya virus (CHIKV) are rapidly emerging viruses that are prevalent in the tropical and subtropical regions of world. Both viruses are transmitted to humans by mosquitoes of the Aedes species, which include the yellow fever mosquito and the Asian tiger mosquito. DENV can cause dengue fever, which is characterized by flu-like symptoms. Also, yearly about 500,000 patients develop more severe dengue, which can be fatal if not properly treated.

CHIKV causes chikungunya fever, with symptoms including high fever, rash, headache, and muscle and joint pain. Approximately 12-49% of CHIKV-infected patients develop chronic debilitating joint pain, which persists from months to years. No specific antiviral treatment or vaccine is available for either of the viruses and treatment is focused on relieving the disease symptoms. For the rational design of vaccines and antiviral drugs it is imperative to better understand the dynamic interactions that occur between the virus and the host during virus reproduction.

The research described in this thesis focuses on the early events in DENV and CHIKV infection. We aimed to further investigate the molecular mechanisms that are involved in viral cell entry. For DENV, we focused on the role of the viral precursor membrane (prM) protein in virus infectivity and how antibodies control the infectious properties of the virus. For CHIKV, we dissected the viral entry pathway and the molecular mechanisms of viral membrane fusion. In addition, we investigated the working mechanism of potent, fusion-inhibitory antibodies against CHIKV.

Dissertation: http://hdl.handle.net/11370/7c4c710d-0bb2-4b84-8040-4795a14e9ee7