Molecular determinants of antigenicity of two subtypes of the tick-borne flavivirus Omsk haemorrhagic fever virus

In 1964, D. H. Clarke defined two antigenic subtypes of Omsk haemorrhagic fever virus (OHFV) based on polyclonal antibody absorption and haemagglutination assays. The current report defines the molecular basis for these antigenic subtypes by comparison of the complete genomes of OHFV strains Kubrin (subtype I) and Bogoluvovska (subtype II). There were six nucleotide differences between these two strains throughout the entire genome and they encoded four amino acid changes including three in the viral envelope (E) protein. Two of these changes were in solvent-exposed regions of domain 3 of the E protein, one of which lies in a region that could easily function in virus-host cell or virus-antibody interactions. These results demonstrate the minimal changes that are required to significantly alter the antigenicity of flaviviruses and also demonstrate the tremendous genetic stability of the tick-borne flaviviruses.