Experimental Assessment of Possible Factors Associated with Tick-Borne Encephalitis Vaccine Failure

Tuchynskaya, Ksenia; Volok, Viktor P.; Illarionova, V. V.; Okhezin, Egor V.; Polienko, Alexandra E.; Belova, Oxana A.; Rogova, Anastasia A.; Chernokhaeva, Liubov L.; Karganova, Galina G.

doi:10.3390/microorganisms9061172

Cited by 14 publications

(16 citation statements)

References 70 publications

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“…Isolation, storage and propagation of the TBEV strains from the laboratory collection of the FSBSI (Chumakov FSC R&D IBP RAS) has been described previously [ 39 , 58 , 59 ]. Viral RNA was isolated using Trireagent LS (Sigma-Aldrich, Burlington, VT, USA) followed by chloroform extraction.…”

Section: Methodsmentioning

confidence: 99%

Activation of Early Proinflammatory Responses by TBEV NS1 Varies between the Strains of Various Subtypes

Starodubova

Tuchynskaya

Kuzmenko

et al. 2023

IJMS

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Tick-borne encephalitis (TBE) is an emerging zoonosis that may cause long-term neurological sequelae or even death. Thus, there is a growing interest in understanding the factors of TBE pathogenesis. Viral genetic determinants may greatly affect the severity and consequences of TBE. In this study, nonstructural protein 1 (NS1) of the tick-borne encephalitis virus (TBEV) was tested as such a determinant. NS1s of three strains with similar neuroinvasiveness belonging to the European, Siberian and Far-Eastern subtypes of TBEV were studied. Transfection of mouse cells with plasmids encoding NS1 of the three TBEV subtypes led to different levels of NS1 protein accumulation in and secretion from the cells. NS1s of TBEV were able to trigger cytokine production either in isolated mouse splenocytes or in mice after delivery of NS1 encoding plasmids. The profile and dynamics of TNF-α, IL-6, IL-10 and IFN-γ differed between the strains. These results demonstrated the involvement of TBEV NS1 in triggering an immune response and indicated the diversity of NS1 as one of the genetic factors of TBEV pathogenicity.

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Section: Methodsmentioning

confidence: 99%

Activation of Early Proinflammatory Responses by TBEV NS1 Varies between the Strains of Various Subtypes

Starodubova

Tuchynskaya

Kuzmenko

et al. 2023

IJMS

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“…Plaque reduction neutralization test (PRNT50) was performed as described earlier (Tuchynskaya et al, 2021) on PEK cell monolayers in 24-well plates. Mouse blood samples were collected via decapitation; serum was separated from the clots by centrifugation and stored in aliquots at -20°C.…”

Section: % Plaque Reduction Neutralization Testmentioning

confidence: 99%

“…Quantitative PCR (qPCR) was carried out using DNA Engine Analyser (BioRad, USA) with a qPCR kit (Syntol, Russia) and specific primers to TBEV and poliovirus (Table S1), as described previously (Tuchynskaya et al, 2021). Viral RNA quantity in the samples was expressed as a decimal logarithm of the genome copy number (GCN) per sample (log 10 GCN/sample), i.e.…”

Section: Detection Of Tbev By Quantitative Pcrmentioning

confidence: 99%

Hybrids of Ixodes ricinus and Ixodes persulcatus ticks effectively acquire and transmit tick-borne encephalitis virus

Belova

Polienko

Averianova

et al. 2023

Front. Cell. Infect. Microbiol.

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Ixodes rici nus and Ixodes persulcatus ticks are the main vectors of tick-borne encephalitis virus (TBEV), which has three main subtypes connected with certain tick species: the European subtype, associated with I. ricinus, and the Siberian and Far-Eastern subtypes, associated with I. persulcatus. Distribution ranges of these species overlap and form large sympatric areas in the East European Plain and Baltic countries. It has previously been shown that crossing of I. ricinus and I. persulcatus is possible, with the appearance of sterile hybrids. Hybridization of ticks can affect not only the spread of ticks but also the properties of natural foci of arbovirus infections, in particular TBEV. In the present study, we analyzed the effectiveness of virus transmission from infected mice to larvae and nymphs and trans-stadial transmission (from larvae to nymph and adult) in I. ricinus, I. persulcatus, and hybrids. For this purpose, we bred a hybrid generation from the crossing of I. persulcatus females and I. ricinus males, and we used the Siberian and European subtypes of TBEV. We showed that after feeding on infected mice, virus prevalence in engorged ticks decreased over time, and after molting, the opposite was true. In hybrids we observed the highest acquisition effectiveness and RNA copy numbers during Siberian TBEV subtype transmission. The efficiency of trans-stadial transmission of both TBEV subtypes was similar in hybrids and parental species. After the second trans-stadial TBEV transmission, a significant increase in ticks’ infection rates was observed only in specific subtype-tick combination. Our data demonstrate the possible features of TBEV circulation in the I. ricinus and I. persulcatus sympatry area.

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“…Genome-wide synteny analysis of the Senzhang strain and three reference strains (Neudoerfl strain for European subtype [22], 205 strain for Far-Eastern subtype [23,24], and Vasilchenko strain for Siberian subtype [12,25]) showed that the Senzhang strain had high synteny with the other three subtypes. However, there was significant variation at the 3' end of the genome sequence.…”

Section: Synteny Analysis Showed Variation At the 3' End Of The Senzh...mentioning

confidence: 99%

The comparative genomic analysis provides insights into the phylogeny and virulence of tick-borne encephalitis virus vaccine strain Senzhang

Zhang

Tian

et al. 2022

PLoS ONE

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Tick-borne encephalitis virus (TBEV) is one of the most dangerous tick-borne viral pathogens for humans. It can cause severe tick-borne encephalitis (TBE), multiple neurological complications, and death. The European subtype (TBEV-Eu), Siberian subtype (TBEV-Sib), and Far-Eastern subtype (TBEV-FE) are three main TBEV subtypes, causing varying clinical manifestations. Though TBEV-FE is the most virulent TBEV subtype, the degree of variation in the amino acid sequence of TBEV polyprotein is not high, leaving an issue without proper explanation. We performed phylogenic analysis on 243 TBEV strains and then took Senzhang strain as a query strain and representative strains of three major TBEV subtypes as reference strains to perform the comparative genomic analysis, including synteny analysis, SNP analysis, InDel analysis, and multiple sequence alignment of their envelope (E) proteins. The results demonstrated that insertions or deletions of large fragments occurred at the 3’ end but not at the 5’ end or in the CDS region of TBEV Senzhang strain. In addition, SNP sites are mainly located in the CDS region, with few SNP sites in the non-coding region. Our data highlighted the insertions or deletions of large fragments at the 3’ end and SNP sites in the CDS region as genomic properties of the TBEV Senzhang strain compared to representative strains with the main subtypes. These features are probably related to the virulence of the TBEV Senzhang strain and could be considered in future vaccine development and drug target screening for TBEV.

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Experimental Assessment of Possible Factors Associated with Tick-Borne Encephalitis Vaccine Failure

Cited by 14 publications

References 70 publications

Activation of Early Proinflammatory Responses by TBEV NS1 Varies between the Strains of Various Subtypes

Activation of Early Proinflammatory Responses by TBEV NS1 Varies between the Strains of Various Subtypes

Hybrids of Ixodes ricinus and Ixodes persulcatus ticks effectively acquire and transmit tick-borne encephalitis virus

The comparative genomic analysis provides insights into the phylogeny and virulence of tick-borne encephalitis virus vaccine strain Senzhang

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