PhD ceremony Ms. J.M. da Silva Voorham: Immature dengue virus: functional properties and potential contribution to disease

PhD ceremony: Ms. J.M. da Silva Voorham, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Immature dengue virus: functional properties and potential contribution to disease

Promotor(s): prof. J.M. Smit, prof. J.C. Wilschut

Faculty: Medical Sciences

Summary:

Dengue virus (DENV) causes the most common mosquito-borne viral infection in the world. According to WHO estimates, 50-100 million dengue virus (DENV) infections occur annually in the subtropical and tropical regions of the world. DENV comprises four serotypes. Each of the serotypes can cause a spectrum of diseases, ranging from a febrile illness to a life-threatening hemorrhagic and vascular permeability syndrome. Most of the patients who develop severe disease have antibodies against different strains of the virus as a result of previous DENV infection episodes. These antibodies not only facilitate more efficient cellular uptake of virions, they also appear to modulate the immune response in infected cells thereby favoring virus particle production. This thesis describes that in the presence of antibodies, non-infectious immature DENV can become highly infectious with titers comparable to standard DENV preparations. During a heterologous secondary DENV infection - so in the presence of cross-reactive antibodies - immature virus particles can contribute to a higher virus titer and act as a co-factor in the pathogenesis of severe disease. In summary, these results show a better understanding of the mechanisms that are important in the process of DENV infection and development of disease. Moreover, these studies have potentially important implications for the development of antiviral agents and safe dengue vaccines.