Characterization of cellular infection of flaviviruses and antigenic properties of their Envelope glycoprotein

Flaviviruses, a leading cause of mosquito borne diseases, comprise of important human pathogens- such as West Nile virus (WNV), Dengue and Zika. With similar clinical manifestation to WNV, Turkey Meningoencephalitis virus (TMEV) is an avian flavivirus that causes a neuro-paralytic disease of domesticated turkeys. There are no vaccines or medications to prevent and treat WNV in humans.

The characterization of the infection-induced intracellular changes and functions is a key step in development of host-defense based remedies. Here we explore the entry and budding process of TMEV and WNV using immunofluorescence microscopy and the associated antigenic features. There is high cross-antigenicity among flaviviruses, with the major immunogen targeted by neutralizing antibodies being the Envelope glycoprotein (E).

E-protein mediates viral penetration through membrane-bilayer fusion in endosomal compartment. Poorly neutralizing cross-species antibodies presumably cause antibody-dependent enhancement of the infection and the disease. A segment of E, the Fusion-Loop, is immune-dominant, and antibodies against it are poorly neutralizing. The Fusion-Loop epitope is buried at the E-dimer interface in the pre-fusion conformation and becomes exposed upon transition into post-fusion. We generate stabilized WNV E-dimers and explore their functional and antigenic properties using acute and convalescent sera sub-pools of WNV patients and animals. We aim to create TMEV antigens for serological, functional and vaccine research. We aim to test WNV and TMEV subunit vaccine prototypes in turkeys animal models. The understanding of the cellular infection of TMEV and WNV, and the antigenic properties of E, will enable the design of new antiviral medications, and possibly a vaccine.