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. 2020 Feb 23;12(2):247.
doi: 10.3390/v12020247.

Tick-Borne Encephalitis Virus: An Emerging Ancient Zoonosis?

Andrei A Deviatkin  1   2 , Ivan S Kholodilov  3 , Yulia A Vakulenko  4   5 , Galina G Karganova  3   6 , Alexander N Lukashev  1   4
Affiliations

Tick-Borne Encephalitis Virus: An Emerging Ancient Zoonosis?

Andrei A Deviatkin et al. Viruses. .

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.

Keywords: Bayesian phylogeny; TBEV; flavivirus; population growth; temporal signal.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Genome layout and TBEV genome fragments represented in GenBank as of June 2019. Y-axis indicates the sequence coverage (the number of known sequences) for each genome position shown in X-axis. (a) Sequences shorter than 100 nucleotides were omitted from the analysis. (b) Sequences shorter than 500 nucleotides were omitted. (c) Sequences shorter than 1000 nucleotides were omitted. (d) The genomic region selected for the phylogenetic analysis is limited by two vertical lines.
Figure 2
Figure 2
(a) Substitution rates among 10 random datasets (50 viruses each) of partial E protein sequences (1028 nt). (b) Root height in 10 random datasets (50 viruses each) of partial E protein sequences (1028 nt). (c) Substitution rates among 10 random datasets (100 viruses each) of partial E protein sequences (1028 nt). (d) Root height in 10 random datasets (100 viruses each) of partial E protein sequences (1028 nt).
Figure 3
Figure 3
(a) Maximum likelihood tree for TBEV species (1028 nt). Black circles indicate high-level nodes that were supported by UFBoot values over 95% [45]. (b) Association between root-to-tip distance and time of isolation for the whole TBEV species.
Figure 4
Figure 4
Association between root-to-tip distance and time of isolation for separated TBEV groups. EUR–European subtype; FE + 886-84-like–Far-Eastern subtype and 886-84 and 178-179 strains; SIB + 2871–Siberian and TBEV-2871 strain; Sib1, Sib2, and Sib3—separated lineages of Siberian subtype.
Figure 5
Figure 5
Bayesian phylogenetic analysis of near-complete E-gene sequences of European TBEV. Branches are color-shaded according to described groups. Tree tips are named according to the region of isolation. Countries or country regions of virus sampling were grouped into nine color-coded geographical regions. Node posterior probabilities above 95% are shown by black circles at the relevant nodes.
Figure 6
Figure 6
Bayesian phylogenetic analysis of near-complete E-gene sequences of Siberian TBEV. Branches are color-shaded according to described groups. Tree tips are named according to region of isolation. Countries or country regions of virus sampling were grouped into six color-coded geographical regions. Node posterior probabilities above 95% are shown by black circles at the relevant nodes.
Figure 7
Figure 7
Bayesian phylogenetic analysis of near-complete E-gene sequences of Far-Eastern TBEV. Branches are color-shaded according to described groups. Tree tips are named according to region of isolation. Countries or country regions of virus sampling were grouped into seven color-coded geographical regions. Node posterior probabilities above 95% are shown by black circles at the relevant nodes.
Figure 8
Figure 8
Pairwise genetic distances for all Eu3 representatives (n = 178), Eu3 from Switzerland (n = 41), and Eu3 from the Czech Republic (n = 35).
Figure 9
Figure 9
Past population dynamics inferred for the three major TBEV subtypes using the Bayesian Skygrid model.
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