TBEV virions are spherical particles with an ,11 kb-RNA genome embedded in a capsid that is surrounded by a lipid envelope mainly containing a virus envelope (E) glycoprotein. This E protein plays a key role in many stages of the virus life cycle; it mediates virus binding to receptors on the cell surface (adsorption) which triggers receptor-mediated endocytosis. Exposure of the endocytosed virus to the acid pH converts the native E protein dimers into fusogenic trimers [18, 19] ; the latter promote fusion of virion and endosomal membranes thus releasing viral RNA into the cytoplasm. The E protein also plays the major role in inducing the host immune response and mediates hemagglutination (HA), i.e. the ability of virions to agglutinate avian erythrocytes; for decades HA has been used in routine diagnosis [20] .