Tick-Borne Encephalitis Virus: An Emerging Ancient Zoonosis?

Abstract

Tick-borne encephalitis (TBE) is one of the most important viral zoonosis transmitted by the bite of infected ticks. In this study, all tick-borne encephalitis virus (TBEV) E gene sequences available in GenBank as of June 2019 with known date of isolation (n = 551) were analyzed. Simulation studies showed that a sample bias could significantly affect earlier studies, because small TBEV datasets (n = 50) produced non-overlapping intervals for evolutionary rate estimates. An apparent lack of a temporal signal in TBEV, in general, was found, precluding molecular clock analysis of all TBEV subtypes in one dataset. Within all subtypes and most of the smaller groups in these subtypes, there was evidence of many medium- and long-distance virus transfers. These multiple random events may play a key role in the virus spreading. For some groups, virus diversity within one territory was similar to diversity over the whole geographic range. This is best exemplified by the virus diversity observed in Switzerland or Czech Republic. These two countries yielded most of the known European subtype Eu3 subgroup sequences, and the diversity of viruses found within each of these small countries is comparable to that of the whole Eu3 subgroup, which is prevalent all over Central and Eastern Europe. Most of the deep tree nodes within all three established TBEV subtypes dated less than 300 years back. This could be explained by the recent emergence of most of the known TBEV diversity. Results of bioinformatics analysis presented here, together with multiple field findings, suggest that TBEV may be regarded as an emerging disease.

Baltic Group Tick-Borne Encephalitis Virus Phylogeography: Systemic Inconsistency Pattern between Genetic and Geographic Distances

“…Unfortunately, there were just two sequences (out of 976 E- gene fragment sequences) from these territories that are publicly available. Both viruses were representatives of the Sib2 TBEV subgroup [ 21 ] (prototype strain Zausaev) collected in the Kirov region. In other words, the current study is limited by fragmentary knowledge of the real Baltic TBEV-Sib distribution.…”

“…We may conclude that some flying animal capable of carrying ticks is a necessary missing link for Baltic TBEV-Sib circulation. According to some estimates, the most recent common ancestor of that subgroup existed just hundreds of years ago [ 21 ]. If Baltic TBEV-Sib could persist without the involvement of migrating animals, most possibly there would have been traces of (re)introduction into Siberia that currently are not observed.…”

“…Phylogenetic data were processed as previously described [ 21 ] with some modifications. Briefly, all available TBEV sequences represented in GenBank as of March 2020 aligning with genome positions 1150–2200 in the reference sequence #NC_001672 were selected ( n = 953).…”

“…Initially, TBEV was subdivided into three major subtypes based on its distribution: European, Siberian, and Far-Eastern subtypes [ 20 ]. In general, the distribution of viruses corresponded to the nominal name, although there were many exceptions [ 21 ]. According to phylogenetical analysis, the Siberian subtype (TBEV-Sib) consists of several TBEV subgroups [ 8 ].…”

TBEV Subtyping in Terms of Genetic Distance

“…Hereinafter, we adhere to the traditional term, subtype, to designate the first taxonomic unit below the TBEV species level. In recent decades, there has been a growing body of evidence that subtypes can be isolated far from their nominal geographic region [8][9][10][11][12][13][14][15][16][17]. Subspecies taxonomy of TBEV was further complicated by the discovery of viruses that could not be unambiguously assigned to known subtypes.…”