The role of antibodies in controlling flavivirus cell entry

PhD ceremony: Mr. B.J.S. Moesker, 12.45 uur, Aula Academiegebouw, Broerstraat 5, Groningen

Dissertation: The role of antibodies in controlling flavivirus cell entry

Promotor(s): prof. J.C. Wilschut

Faculty: Medical Sciences

Dengue virus (DENV) and West Nile virus (WNV) are emerging mosquito-borne viral pathogens. The past decades have witnessed a global resurgence of DENV, now causing an estimated 50 million infections annually. Although most dengue cases are asymptomatic, infection may result in dengue fever, a debilitating febrile illness, or progress into more severe manifestations known as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). WNV is common in regions throughout the Old World and Oceania where it causes incidental outbreaks associated with only minor illness. However, a more virulent strain of WNV recently emerged in North America, involving high numbers of neuroinvasive disease with fatality rates of ±10% amongst hospitalized patients. Currently, no vaccines or antiviral drugs are available to prevent or treat disease caused by DENV or WNV.

Antibodies (Abs) play a central role in controlling flavivirus infections. Individuals that have undergone flavivirus infection are protected upon reinfection due to the presence of protective Abs. At the same time, the presence of Abs may predispose individuals to more severe disease upon infection with DENV. A more fundamental insight into the molecular basis of protection against flavivirus infection is crucial for the development of antiviral strategies. Therefore, the studies described in this thesis focus on the role of antibodies in the cellular entry of flaviviruses, with the ultimate aim to gain a better understanding of the mechanisms of Ab-mediated neutralization and enhancement of flavivirus infection.