The mutant IC-D67G was distinct from other HA-deficient TBEV strains since there was no obvious correlation between loss of HA activity and significantly reduced growth in mammalian cells. The Yar 71 virus, with the corresponding D67G mutation was isolated from a fatally infected individual (Table 1 ) and ominously, similar substitutions have also been detected in other TBEV isolates from hospitalised patients with encephalitis (Table 2 ). It is possible that due to altered surface charge and hydrophobicity, strains with D67G might be more able to penetrate the human blood-brain barrier (neuroinvasiveness) or more rapidly spread between human neurones, with no correlation to reduced mouse neuroinvasiveness. This would explain the recently discovered association of the most severe form of human encephalitis with the SIB strains [17] .