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Host cell responses to dengue virus infection

PhD ceremony:Ms M.A. (Mayra) Diosa Toro
When:September 11, 2017
Supervisors:prof. dr. J.M. (Jolanda) Smit, prof. dr. S. Urcuqui Inchima
Where:Academy building RUG
Faculty:Medical Sciences / UMCG
Host cell responses to dengue virus infection

Dengue virus (DENV) is the most common mosquito-borne virus  and annually around 390 million people get infected with major socio-economic consequences. In spite of this, there are no specific therapies available. With the research presented in the PhD thesis “host cell responses to dengue virus infection” we aimed to better understand the molecular interactions occurring between DENV and its human host cells. In our research we determined which human cell types are more likely to be infected by DENV upon the mosquito bite. We found that macrophages, an important immune cell which function is to kill invading microorganism, actually contribute in great manner to the replication of DENV. Furthermore, we deciphered one of the mechanisms by which antibodies against DENV can, instead of controlling the virus, enhance the infection of human macrophages. We also studied how human small RNA molecules, that are in charge of controlling the expression of many genes, are altered by DENV. We described the mechanism by which one of these small RNA molecules reduces the replication of DENV. Finally we studied how DENV is able to regulate the cellular stress induced in infected cells in order to promote its own survival. Thus, with this thesis we deepened the knowledge regarding the mechanisms by which human cells interact with DENV. The detailed study of such interactions will guide the rational design of anti-dengue therapies. Indeed, during our studies we discovered a potential anti-DENV drug and its antiviral activity is also shown in this thesis.