Whilst most strains of TBEV show HA activity, during the past 10 years atypical HA-deficient strains have been isolated with increasing frequency in Europe from both ticks and infected patients. More than 40 HA-deficient strains are now recognized and they all exhibit reduced pathogenicity for mice when compared with HA-competent strains. They are also called ''antigenically deficient'' (AD) strains, in contrast to the more common antigenically competent (AC) strains; the term ''AD'' is derived from the strict correlation between loss of HA and immunoprecipitating activities [21] . The AD-viruses were also deficient in complement-fixation and neutralization tests when analysed using either hyperimmune antisera or sera obtained from patients recovered from TBE [21] . Here, using molecular methods of analysis, we show that HA-deficiency is linked with the adaptation of SIB TBEV strains to western European Ixodes ricinus ticks reflecting altered, E protein-mediated, receptor/fusion functions. We also illustrate how this might result in continued westward dispersal and emergence of new highly pathogenic virus variants (see Fig. S1 ).