Inferring Evolutionary Timescale of Omsk Hemorrhagic Fever Virus.

Until 2020, there were only three original complete genome (CG) nucleotide sequences of Omsk hemorrhagic fever virus (OHFV) in GenBank. For this reason, the evolutionary rate and divergence time assessments reported in the literature were based on the E gene sequences, but notably without temporal signal evaluation, such that their reliability is unclear. As of July 2022, 47 OHFV CG sequences have been published, which enables testing of temporal signal in the data and inferring unbiased and reliable substitution rate and divergence time values. Regression analysis in the TempEst software demonstrated a stronger clocklike behavior in OHFV samples for the complete open reading frame (ORF) data set (R2 = 0.42) than for the E gene data set (R2 = 0.11). Bayesian evaluation of temporal signal indicated very strong evidence, with a log Bayes factor of more than 5, in favor of temporal signal in all data sets. Our results based on the complete ORF sequences showed a more precise OHFV substitution rate (95% highest posterior density (HPD) interval, 9.1 × 10-5-1.8 × 10-4 substitutions per site per year) and tree root height (416-896 years ago) compared with previous assessments. The rate obtained is significantly higher than tick-borne encephalitis virus by at least 3.8-fold. The phylogenetic analysis and past population dynamics reconstruction revealed the declining trend of OHFV genetic diversity, but there was phylogenomic evidence that implicit virus subpopulations evolved locally and underwent an exponential growth phase.

Delimitation of the tick-borne flaviviruses. Resolving the tick-borne encephalitis virus and louping-ill virus paraphyletic taxa.

The tick-borne flavivirus (TBFV) group contains at least 12 members where five of them are important pathogens of humans inducing diseases with varying severity (from mild fever forms to acute encephalitis). The taxonomy structure of TBFV is not fully clarified at present. In particular, there is a number of paraphyletic issues of tick-borne encephalitis virus (TBEV) and louping-ill virus (LIV). In this study, we aimed to apply different bioinformatic approaches to analyze all available complete genome amino acid sequences to delineate TBFV members at the species level. Results showed that the European subtype of TBEV (TBEV-E) is a distinct species unit. LIV, in turn, should be separated into two species. Additional analysis of TBEV and LIV antigenic determinant diversity also demonstrate that TBEV-E and LIV are significantly different both from each other and from the other TBEV subtypes. The analysis of available literature provided data on other virus phenotypic particularities that supported our hypothesis. So, within the TBEV + LIV paraphyletic group, we offer to assign four species to get a more accurate understanding of the TBFV interspecies structure according to the modern monophyletic conception.

Phylogeography and Re-Evaluation of Evolutionary Rate of Powassan Virus Using Complete Genome Data.

In this paper, we revealed the genetic structure and migration history of the Powassan virus (POWV) reconstructed based on 25 complete genomes available in NCBI and ViPR databases (accessed in June 2021). The usage of this data set allowed us to perform a more precise assessment of the evolutionary rate of this virus. In addition, we proposed a simple Bayesian technique for the evaluation and visualization of 'temporal signal dynamics' along the phylogenetic tree. We showed that the evolutionary rate value of POWV is 3.3 × 10-5 nucleotide substitution per site per year (95% HPD, 2.0 × 10-5-4.7 × 10-5), which is lower than values reported in the previous studies. Divergence of the most recent common ancestor (MRCA) of POWV into two independent genetic lineages most likely occurred in the period between 2600 and 6030 years ago. We assume that the divergence of the virus lineages happened due to the melting of glaciers about 12,000 years ago, which led to the disappearance of the Bering Land Bridge between Eurasia and North America (the modern Alaskan territory) and spatial division of the viral areal into two parts. Genomic data provide evidence of the virus migrations between two continents. The mean migration rate detected from the Far East of Russia to North America was one event per 1750 years. The migration to the opposite direction occurred approximately once per 475 years.

Fox rabies outbreaks in the republic of Buryatia: Connections with neighbouring areas of Russia, Mongolia and China.

The Republic of Buryatia (RB) is located southeast of Lake Baikal and shares a long border with Mongolia. This region of Russia was rabies-free from 1982 to 2010. The first outbreak of fox rabies in RB was identified in 2011, about 30 km from the Russian-Mongolian border. We assessed the possible pathways to further spread the 'steppe' phylogenetic lineage of the rabies virus near the northeastern limits of its known distribution. All rabies cases were located 30-210 km north of the Russia-Mongolia border, with a distance of up to 320 km from each other. Rabies has spread to the north across steppe landscapes and river valleys, with foxes being the main natural hosts of the infection. All RABV isolates from RB belong to the 'steppe' phylogenetic lineage, and three major phylogenic groups could be separated. Group 1 contains sequences from RB, Mongolia, China (Inner Mongolia), and bordering regions of Russia. Group 2 is formed by isolates from other regions of Eastern Siberia, which have no borders with RB and foreign countries. Group 3 contains samples from Western Siberia with endemic fox rabies since the 1950s. The most probable cause of fox rabies epizooty in the RB was multiple drift of the RABV across the Russian-Mongolian border. Our data show that after 2010, fox rabies affected new areas in Central Asia and extended to the north and northeast. Affected areas are similar to the Mongolian-type steppes in their zoogeographical aspect. Closely related genetic lineages of RABV are circulating in RB, Mongolia and the nearest areas of China. International cooperation is necessary to prevent the spread of rabies in the bordering territories of these countries.

Reporting of New tick-borne encephalitis virus strains isolated in Eastern Siberia (Russia) in 1960-2011 and explaining them in an evolutionary context using Bayesian phylogenetic inference.

Tick-borne encephalitis virus (TBEV) is one of the main tick-borne viral pathogens of humans. Infection may induce signs of meningitis, encephalitis, paralysis and high fever. TBEV is well studied by molecular phylogenetic methods. The present-day implementation of Bayesian phylogenetic models allows population dynamics to be tracked, providing changes in population size that were not directly observed. However, the description of the past population dynamics of TBEV is rare in the literature. In our investigation, we provide data on the dynamics of viral genetic diversity of TBEV in Zabaikalsky Krai (Eastern Siberia, Russia) revealed by the Bayesian coalescent inference in a BEAST program. As a data set, we used the envelope (E) protein partial gene sequences (1308 nt) of 38 TBEV strains (including six "886-84-like" or Baikalian subtype strains (TBEV-B)), isolated in Zabaikalsky Krai (Eastern Siberia, Russia) in 1960-1963 and 1995-2011. To increase estimations reliability, we compared 9 model combinations by Path sampling and Stepping-stone sampling methods. It has been shown that the genetic diversity decline in the population history of TBEV in the 1950s coincides with the date of the beginning of wide dichlorodiphenyltrichloroethane forest dusting in Siberia. We assumed that the TBEV population on the territory of Siberia went through a genetic bottleneck. Also, we provide data estimating the divergence time of TBEV-B strains and indicate the specific evolution rate of an ancestor lineage of the Baikalian subtype, illustrated on a phylogenetic tree, and reconstructed under a relaxed clock model.

"886-84-like" tick-borne encephalitis virus strains: Intraspecific status elucidated by comparative genomics.

Tick-borne encephalitis virus (TBEV) can cause severe meningitis, encephalitis, and meningoencephalitis. TBEV represents a pathogen of high zoonotic potential and an emerging global threat. There are three known subtypes of TBEV: Far-Eastern, Siberian and European. Since 2001 there have been suggestions that two new subtypes may be distinguished: "178-79" and "886-84". These assumptions are based on the results of the envelope gene fragment sequencing (Zlobin et al., 2001; Kovalev and Mukhacheva, 2017) and genotype-specific probes molecular hybridization (Demina et al., 2010). There is only one full-genome sequence of "178-79" strain and two identical ones of "886-84" strain can be found in GenBank. For clarification of the intraspecific position of the "886-84-like" strains group we completely sequenced six previously unknown "886-84-like" strains isolated in Eastern Siberia. As a result of applying different bioinformatics approaches, we can confirm that "886-84-like" strains group is a distinct subtype of TBEV.

Complete Genome Sequences of Four European Subtype Strains of Tick-Borne Encephalitis Virus from Eastern Siberia, Russia.

Three tick-borne encephalitis virus (TBEV) strains were isolated from Ixodes persulcatus ticks, and one was isolated from a shrew in the territory of eastern Siberia (Russia). The level of sequence identity compared to Neudoerfl (the European prototype strain) is 97.2 to 97.3%.