A panel of deoxyoligonucleotide probes for studying the genetic variability and genotyping of Tick-borne encephalitis virus (TBEV) strains by molecular hybridization of nucleic acids (MHNA) was created. This panel allows to estimate the genetic structure of individual TBEV strains, as the targets for probes are both variable and genotype (subtype)-specific sequences of all TBEV genes. With the help of this panel using the method of molecular hybridization of nucleic acids 268 archived TBEV isolates were investigated and the distribution of its genotypes and subgenotypes of genotype 3 was made more precise in the territory of Eurasia. The conclusion made earlier has confirmed that five genotypes of TBEV co-circulate in Eastern Siberia. It is generally recognized that the Far Eastern (TBE-FE), European (TBE-Eu), and Siberian (TBE-Sib) genotypes are widespread and epidemiologically important. The fourth genotype is presented by only one isolate, TBE178-79, originated from Irkutsk region, Russia. The fifth genotype includes 10 isolates, 1 of them, TBE886-84, was found earlier and recognized as unique [Zlobin et al. (2001b): Vopr Virusol 1:12-16 (Russian)].
Background. During the study of the genetic variability of the tick-borne encephalitis virus (TBEV) in Eastern Siberia, a group of 22 strains with a unique genetic structure significantly different from all known TBEV subtypes was identified. This TBEV variant was tentatively called “group 886”. Therefore, for this original TBEV variant it was necessary to study the genetic, biological properties of the “group 886” strains, clarify its TBEV taxonomic status, its range, evolutionary history, etc.Aim. The generalization of the currently available data on genetic and biological properties of TBEV “886” group.Materials and methods. The genetic structure of “group 886” strains was studied by the complex of molecular-genetic methods (MHNA, sequencing of fragments or the complete genome).Results. It was shown that “group 886” strains form a separate cluster on phylogenetic tree, and the level of genetic differences from other genotypes is more than 12 %. It was defined that this TBEV variant has its own area (Irkutsk region, Republic of Buryatia, Trans-Baikal region, Northern Mongolia). Its ecological connection with all links of the transmissive chain (ixodid ticks, small mammals, human), participation in human pathology, stability and duration of circulation in the Baikal region, individual evolutionary history were proved. Some phenotypic characteristics of the “group 886” strains were considered.Conclusion. The presented data testify to the validity of the “886 group” isolation as an independent genetic type. Taking into account the geographical distribution of this TBEV genotype, we propose to assign it the name “Baikal genotype/subtype”.
Tick-borne encephalitis virus (TBEV) is the most important tick-transmitted pathogen. It belongs to the
Flaviviridae
family and causes severe human neuroinfections. In this study, protective efficacy of the chimeric antibody chFVN145 was examined in mice infected with strains belonging to the Far-Eastern, European, and Siberian subtypes of TBEV, and the antibody showed clear therapeutic efficacy when it was administered once one, two, or three days after infection. The efficacy was independent of the TBEV strain used to infect the mice; however, the survival rate of the mice was dependent on the dose of TBEV and of the antibody. No enhancement of TBEV infection was observed when the mice were treated with non-protective doses of chFVN145. Using a panel of recombinant fragments of the TBEV glycoprotein E, the neutralizing epitope for chFVN145 was localized in domain III of the TBEV glycoprotein E, in a region between amino acid residues 301 and 359. In addition, three potential sites responsible for binding with chFVN145 were determined using peptide phage display libraries, and 3D modeling demonstrated that the sites do not contact the fusion loop and, hence, their binding with chFVN145 does not result in increased attachment of TBEV to target cells.
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