Peculiarities of interaction of high and low virulent strains of tick-borne Encephalitis virus of the Far Eastern subtype with human blood leukocytes

In this work, it was necessary to show the first stage of the interaction of the tick-borne encephalitis virus with blood cells, during which the selection of virus strains capable of successful assembly of virions occurs.The aim of the work: to show ex vivo the features of interaction of strains TBEV with different molecular genetic structure and virulence with human blood leukocytes.Materials and methods. The donor’s venous blood was infected ex vivo with the TBEV using the highly virulent strain Dal’negorsk and the low-virulent strain Primorye-437. Virus accumulation in experimental blood samples was observed after 15 min, 30 min, 1 h, and 24 h of exposition. The indication of the virus, shown by different methods of laboratory diagnostics (ELISA, PCR, IFA, titer of the infectious virus), made it possible to identify the characteristic features of the initial stage of the infectious process caused by these strains TBEV.Conclusion. The highly pathogenic strain Dal‘ has demonstrated the ability to quickly penetrate into leukocytes in 15 minutes, and, therefore, at the initial stage of the infectious process, to implement the mechanisms of its “escape” from immune supervision. The low-virulent strain P-437, on the contrary, showed the ability to stay on the surface of leukocytes for a long time, penetrating into them only after 24 hours of exposure, immediately influencing the cells of the immune system, which can lead to rapid elimination of the virus from the body.

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CHARACTERISTICS OF THE FAR EASTERN POPULATION OF TICK-BORNE ENCEPHALITIS VIRUS AND SOLVING ISSUES OF SPECIFIC PREVENTION

Acta biomedica scientifica ◽

10.29413/abs.2018-3.4.7 ◽

2018 ◽

Vol 3 (4) ◽

pp. 42-46

Author(s):

G. N. Leonova

Keyword(s):

Virulent Strain ◽

Biological Properties ◽

Encephalitis Virus ◽

Viral Population ◽

Full Genome Sequencing ◽

Genetic Characteristics ◽

Specific Antibodies ◽

Tick Borne Encephalitis ◽

Tick Borne Encephalitis Virus ◽

Far Eastern

The subdivision of the viral population into subtypes and clusters based on the molecular genetic characteristics of the tick-borne encephalitis virus (TBEV) strains predetermines not only the differences in the biological properties of these strains, but also their different responses to specific antibodies in persons vaccinated against TBE.The aim of the present study is to show the differences in biological properties on the model of two strains of Far Eastern TBEV subtype belonging to different clusters and to substantiate the need for a personalized approach to the vaccine prophylaxis of tick-borne encephalitis.Results. Two strains of TBEV were used in the studies. On the basis of full genome sequencing the Dal’negorsk strain (FJ402886, GenBank) is referred to the typical representative of Sofjin-like, and Primorye-437 (JQ825162, GenBank) – to Oshima-like TBEV strains of the Far Eastern subtype.The experiment shows the levels of specific antibodies capable of neutralizing virulence strains of tick- borne encephalitis virus. Low antibody titers (1:100 and 1:400) can neutralize only a low dose of a non-virulent strain of tick-borne encephalitis virus. Reliable protection against the disease of people infected with virulent strains of the TBEV can provide only a high level of specific antibodies.Conclusion. If the level of specific antibodies of IgG is 1:400 or lower, the vaccination course should be continued, at a titer of antibodies above 1:400, revaccination can be postponed subject to annual monitoring of specific immunity parameters in the pre-epidemic TBE season.

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Comprehensive assessment of specific antibodies on infectious activity of tick-borne encephalitis virus

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-2019-3-4-559-567 ◽

2019 ◽

Vol 9 (3-4) ◽

pp. 559-567

Author(s):

G. N. Leonova ◽

O. S. Majstrovskaya ◽

V. A. Lubova ◽

N. B. Sanina

Keyword(s):

Ex Vivo ◽

Experimental Studies ◽

Encephalitis Virus ◽

Virus Elimination ◽

Specific Antibodies ◽

Tick Borne Encephalitis ◽

Antibody Titers ◽

Tick Borne Encephalitis Virus

Vaccines for prophylactic immunization provide the most reliable and effective protection against the vast majority of infectious diseases. Tick-borne encephalitis (TBE) represents a high-priority medical issue at the territory of the Eurasian continent. Of great importance is assessing a role of distinct antibody titers especially low titers, observed quite often in vaccinated individuals, sometimes posing obstacles in determining a threshold of seropositivity as well as the level of specific protection against TBE virus. We aimed at obtaining data to assess antiviral activity of virus-specific antibodies with distinct titer levels based on the in vitro, ex vivo and in vivo experimental studies with a highly virulent Far-Eastern strain of tick-borne encephalitis virus. The in vitro, ex vivo and in vivo comprehensive experimental studies with a highly virulent Far-Eastern strain of tick-borne encephalitis virus (TBEV) were conducted and the dynamics of antiviral activity of virus-specific antibodies at variable titers (1:100–1:3200) was measured (timeframe ranged within 1–96 hours p.i.) to provide a rationale for evaluating the antiviral immune response. It was found that the in vitro experiments demonstrated that the IgG at 1:100 titer exerted a weak anti-TBEV neutralizing effect at all time-points examined. The IgG 1:400 titer caused a 2 log PFU/mL decline in TBEV Dal strain yield at 72 h post-infection, whereas at 1:3200 titer it completely suppressed TBEV replication throughout the observation period. The ex vivo experiments with blood serum obtained from vaccinated subjects demonstrating a range of TBEV antibody titers (sera from vaccinated individuals with varying anti-TBEV antibody titers) and in vivo (outinbred white mice) experiments revealed a delayed virus elimination for antibody titers at 1:100 and 1:200 as well as rapid virus elimination (1–2 days p.i.) for antibody titers greater than 1:400. Thus, antibody titer at 1:400 may be considered as the universal anti-TBEV protection threshold. In order to properly conclude regarding the revaccination schedule it is advised to start with testing blood serum for durability of anti-TBEV immune response. Subjects with TBEV antibody titers at 1:100 and 1:200 should be strongly recommended to undergo a mandatory revaccination. Such an approach is believed to be the most effective way toward enhancing efficacy of vaccine-mediated protection against TBE.

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Tick-Borne Encephalitis Virus Adaptation in Different Host Environments and Existence of Quasispecies

Viruses ◽

10.3390/v12080902 ◽

2020 ◽

Vol 12 (8) ◽

pp. 902

Author(s):

Renata Helmová ◽

Václav Hönig ◽

Hana Tykalová ◽

Martin Palus ◽

Lesley Bell-Sakyi ◽

...

Keyword(s):

Virulent Strain ◽

Encephalitis Virus ◽

Genome Sequences ◽

Tick Borne Encephalitis ◽

Ricinus Tick ◽

Tick Borne Encephalitis Virus ◽

Genomic Regions ◽

Virus Adaptation ◽

Virus Survival ◽

Highly Virulent

A highly virulent strain (Hypr) of tick-borne encephalitis virus (TBEV) was serially subcultured in the mammalian porcine kidney stable (PS) and Ixodes ricinus tick (IRE/CTVM19) cell lines, producing three viral variants. These variants exhibited distinct plaque sizes and virulence in a mouse model. Comparing the full-genome sequences of all variants, several nucleotide changes were identified in different genomic regions. Furthermore, different sequential variants were revealed to co-exist within one sample as quasispecies. Interestingly, the above-mentioned nucleotide changes found within the whole genome sequences of the new variants were present alongside the nucleotide sequence of the parental strain, which was represented as a minority quasispecies. These observations further imply that TBEV exists as a heterogeneous population that contains virus variants pre-adapted to reproduction in different environments, probably enabling virus survival in ticks and mammals.

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Antiviral Activity of Uridine Derivatives of 2-Deoxy Sugars against Tick-Borne Encephalitis Virus

Molecules ◽

10.3390/molecules24061129 ◽

2019 ◽

Vol 24 (6) ◽

pp. 1129 ◽

Cited By ~ 1

Author(s):

Ewelina Krol ◽

Ilona Wandzik ◽

Gabriela Brzuska ◽

Luděk Eyer ◽

Daniel Růžek ◽

...

Keyword(s):

Antiviral Activity ◽

Virulent Strain ◽

Encephalitis Virus ◽

Antiviral Therapies ◽

Tick Borne Encephalitis ◽

Tbev Strain ◽

Ic50 Values ◽

Tick Borne Encephalitis Virus ◽

Derivatives Of ◽

Deoxy Sugars

Tick-borne encephalitis virus (TBEV) is a causative agent of tick-borne encephalitis (TBE), one of the most important human infections involving the central nervous system. Although effective vaccines are available on the market, they are recommended only in endemic areas. Despite many attempts, there are still no specific antiviral therapies for TBEV treatment. Previously, we synthesized a series of uridine derivatives of 2-deoxy sugars and proved that some compounds show antiviral activity against viruses from the Flaviviridae and Orthomyxoviridae families targeting the late steps of the N-glycosylation process, affecting the maturation of viral proteins. In this study, we evaluated a series of uridine derivatives of 2-deoxy sugars for their antiviral properties against two strains of the tick-borne encephalitis virus; the highly virulent TBEV strain Hypr and the less virulent strain Neudoerfl. Four compounds (2, 4, 10, and 11) showed significant anti-TBEV activity with IC50 values ranging from 1.4 to 10.2 µM and low cytotoxicity. The obtained results indicate that glycosylation inhibitors, which may interact with glycosylated membrane TBEV E and prM proteins, might be promising candidates for future antiviral therapies against TBEV.

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Coding nucleotide sequences of tick-borne encephalitis virus strains isolated from human blood without clinical symptoms of infection

Russian Journal of Genetics ◽

10.1134/s1022795410030087 ◽

2010 ◽

Vol 46 (3) ◽

pp. 315-322 ◽

Cited By ~ 6

Author(s):

S. I. Belikov ◽

G. N. Leonova ◽

I. G. Kondratov ◽

E. V. Romanova ◽

E. V. Pavlenko

Keyword(s):

Human Blood ◽

Clinical Symptoms ◽

Nucleotide Sequences ◽

Encephalitis Virus ◽

Tick Borne Encephalitis ◽

Tick Borne Encephalitis Virus ◽

Virus Strains

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TBE in South Korea

Tick-borne encephalitis - The Book ◽

10.33442/978-981-14-0914-1_12b-31 ◽

2019 ◽

Author(s):

Joon Young Song

Keyword(s):

South Korea ◽

Human Case ◽

Encephalitis Virus ◽

Surveillance Studies ◽

Tick Borne Encephalitis ◽

Tick Borne Encephalitis Virus

Although no human case of tick-borne encephalitis (TBE) has been documented in South Korea to date, surveillance studies have been conducted to evaluate the prevalence of tick-borne encephalitis virus (TBEV) in wild ticks.

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