For many viruses, HA-activity is recognised as a reflection of receptor [35] [36] [37] or low-pH dependent fusion activity [38, 39] . It was suggested that HA activity of flaviviruses is mediated by fusion activity of the E protein [32] because it is optimal at pH 6.2 which promotes conversion of native E protein dimers into fusion-active trimers [18, 19] . This implies that the Yar mutations identified herein destabilise trimer-trimer contacts or contact between trimers and erythrocyte membranes, thus preventing HA activity. Alternatively, these mutations may impact on both E protein functions, ie virus adsorption to the cell surface and pH-dependent fusion of virions with endosomal membranes. Therefore, depending on charge and hydrophobicity, tick cell receptors may restrict ''easy'' entry of WE-strains into I. persulcatus or SIB-strains into I. ricinus. Clearly these barriers to infection are not absolute since Vs virus (SIB TBEV) has a limited capacity to replicate in I. ricinus (Fig. 5 ). Phylogenetic analysis also supports our hypothesis; it was proposed that WE-strains diverged from ancestral FE-and SIB lineages [40] , implying that the emergent WE subtype adapted to I. ricinus from I. persulcatus by evolving a more hydrophobic E protein (Fig. 2) . The coincidence of increased hydrophobicity of the virion surface for I. ricinus-adapted WEstrains and SIB Yar viruses presumably reflects a similar molecular requirement for different viruses to adapt to the same host. Alternatively, the emergence of the atypical Yar viruses may result from adaptation of TBEV to both tick species. Indeed SIB TBEV strains have been isolated from both I. ricinus and I. persulcatus on numerous occasions [11, 34] and regular switching between them cannot be excluded. These data might explain the apparently increasing dissemination of SIB TBEV in Europe; in a few decades this virus could reach more western territories, possibly even the UK where I. ricinus is the vector for the Louping ill virus that is closely related to TBEV.