Tick-borne encephalitis virus: reference strain Sofjin and problem of its authenticity

Abstract

The Sofjin strain is one of the first isolates of tick-borne encephalitis virus and, due to its wide distribution in virus collections, it has become the reference strain. Until now, GenBank has recorded several sequences associated with the Sofjin strain that have significant differences between each other. We have sequenced the complete genome of the Sofjin strain from a virus collection and a genome fragment of the two vaccine Sofjin strains. According to phylogenetic analysis, we concluded that the GenBank sequences belong to three independent groups of Sofjin strains of the Far Eastern subtype. Their genetic differences are not a result of microevolution associated with numerous passages. Retrospective analysis of the peculiarities of origin and distribution for each of these groups showed the authenticity of one of them. For the first time, we have determined a complete genome sequence of the authentic reference TBEV strain Sofjin. Two other groups of strains named Sofjin were probably the result of cross-contamination or laboratory error. The high probability of contamination requires the introduction of a new standard for virological laboratories, the key point of which is the obligatory genetic identification of all collection strains.

Genetic description of a tick-borne encephalitis virus strain Sofjin with the longest history as a vaccine strain

“…The phylogenetic analysis of GenBank nucleotide sequences of protein E encoding genome fragments of Far-Eastern TBEV strains (Fig. 2 ) showed, as mentioned previously (Kovalev et al 2012 ), that ‘Sofjin’ strains did not form a distinct branch on this tree. The E protein sequence of Sofjin-Chumakov was identical to the one of the TBEV strain SofjinKGG (Kozlovskaya et al 2010 ).…”

“…The complete genome sequence was presented only in (Pletnev et al 1990 ). Over the next 20 years, more sequences appeared, describing the nucleotide composition of the strains called Sofjin (Kovalev et al 2012 ), drastically differing one sequence from one another. This fact arouses the necessity for the description of the strain Sofjin particularly used for the TBE vaccine produced in Moscow.…”

“…Strain SofjinKSY_JF819648 (D.I. Ivanovsky Institute of Virology) (Kovalev et al 2012 ) contained only five nucleotide substitutions to the Sofjin-Chumakov sequence. Possibly, these differences could be the result of different passage histories of these viruses.…”

“…Sequence SofjinVM2001_JF819650 showed a significant difference from the sequence Sofjin-Chumakov, despite the fact that its authors claimed it to be sequenced from a drugstore-bought vial of TBE vaccine Moscow (Kovalev et al 2012 ). It could be due to formalin inactivation damage to the viral RNA that finally caused various nucleotide mismatches during RT-PCR reactions before sequencing or any other laboratory artifacts.…”

Structure‐guided Discovery of a Novel Non‐peptide Inhibitor of Dengue Virus NS2B–NS3 Protease

“…Dengue fever is caused by dengue virus (DENV) serotypes 1–4, which belong to the Flavivirus genera . The virion contains a positive‐sense single‐stranded RNA which encodes a polyprotein that is subsequently processed into three structural proteins and seven non‐structural proteins (NS1, 2A, 2B, 3, 4A, 4B and 5) by the action of host and viral proteases .…”