Variability in the 3′ untranslated regions of the genomes of the different tick-borne encephalitis virus subtypes

Tick-borne encephalitis viruses (TBEVs) are usually divided into three major subtypes: European (TBEV-Eu), Siberian (TBEV-Sib) and Far Eastern (TBEV-FE). The TBEV-Eu strains have the longest genomes, and TBEV-FE strains have the smallest genomes. Changes in the variable region of the untranslated region (V3′ UTR) play a major role in determining the viral genome length. Analyses of the 3′ UTRs of the different subtypes of TBEV have revealed significant changes in the secondary structures of the V3′ UTR of TBEV. More complex secondary structures of the V3′ UTR regions are typical for TBEV-Eu. The Siberian strain Tomsk-PT122 was isolated from birds and has an unusual 3′ UTR. Several short fragment (24–26 nucleotides) insertions derived from the viral E (2) and NS4a (1) genes have been found in the V3′ UTR of Tomsk-PT122. Additionally, the length of the V3′ UTR increases from 21 to 37 nucleotides during passages of the C11-13 strain of TBEV-Sib into PEK, 293 and Neuro-2a cells. The elongation of the V3′ UTRs of Tomsk-PT122 and C11-13 is the first direct evidence of an intragenomic 3′ UTR modification (insertion) for TBEV. Thus, the obtained results suggest that changing the length of the V3′ UTR in the genome is typical for different TBEV subtypes and can play an essential role in effective TBEV replication in different host cells.