Recovery of a Far-Eastern Strain of Tick-Borne Encephalitis Virus with a Full-Length Infectious cDNA Clone

A stable full-length infectious cDNA clone of the Oshima strain of Tick-borne encephalitis virus (Far-Eastern subtype) was developed by a long high-fidelity RT-PCR and one-step cloning procedure. The infectious clone (O-IC) had four amino acid substitutions and produced smaller plaques when compared with the parent Oshima 5-10 strain. Using site-directed mutagenesis, the substitutions were reverted to restore the parent virus sequence (O-IC-pt). Although genetically identical, parent virus Oshima 5-10 and virus recovered from O-IC-pt demonstrated some biological differences that are possibly explained by the presence of quasispecies with differing virulence characteristics within the original virus population. These observations may have implications for vaccines based on modified infectious clones. It was also demonstrated that the amino acid substitution E-S40→P at position 40 in the envelope (E) glycoprotein was responsible for plaque size reduction, reduced infectious virus yields in cell culture and reduced mouse neurovirulence. Additionally, two amino acid substitutions in the non-structural (NS)5 protein (virus RNA-dependent RNA polymerase) NS5-V378→A and NS5-R674→K also contributed to attenuation of virulence in mice, but did not demonstrate a noticeable biological effect in baby hamster kidney cell culture. Comparative neurovirulence tests revealed how the accumulation of individual mutations (E-S40→P, NS5-V378→A and NS5-R674→K) can result in the attenuation of a virus.

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Computational and Rational Design of Single-Chain Antibody against Tick-Borne Encephalitis Virus for Modifying Its Specificity

Viruses ◽

10.3390/v13081494 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1494

Author(s):

Ivan K. Baykov ◽

Pavel Y. Desyukevich ◽

Ekaterina E. Mikhaylova ◽

Olga M. Kurchenko ◽

Nina V. Tikunova

Keyword(s):

Rational Design ◽

Fold Increase ◽

Encephalitis Virus ◽

Chimeric Antibody ◽

Single Chain ◽

Single Chain Antibody ◽

Glycoprotein E ◽

Tick Borne Encephalitis ◽

Tick Borne Encephalitis Virus ◽

Far Eastern

Tick-borne encephalitis virus (TBEV) causes 5−7 thousand cases of human meningitis and encephalitis annually. The neutralizing and protective antibody ch14D5 is a potential therapeutic agent. This antibody exhibits a high affinity for binding with the D3 domain of the glycoprotein E of the Far Eastern subtype of the virus, but a lower affinity for the D3 domains of the Siberian and European subtypes. In this study, a 2.2-fold increase in the affinity of single-chain antibody sc14D5 to D3 proteins of the Siberian and European subtypes of the virus was achieved using rational design and computational modeling. This improvement can be further enhanced in the case of the bivalent binding of the full-length chimeric antibody containing the identified mutation.

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Ability of inactivated vaccines based on far‐eastern tick‐borne encephalitis virus strains to induce humoral immune response in originally seropositive and seronegative recipients

Journal of Medical Virology ◽

10.1002/jmv.25316 ◽

2018 ◽

Vol 91 (2) ◽

pp. 190-200 ◽

Cited By ~ 8

Author(s):

Galina B. Maikova ◽

Liubov L. Chernokhaeva ◽

Yulia V. Rogova ◽

Liubov I. Kozlovskaya ◽

Ivan S. Kholodilov ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Encephalitis Virus ◽

Humoral Immune ◽

Tick Borne Encephalitis ◽

Inactivated Vaccines ◽

Tick Borne Encephalitis Virus ◽

Far Eastern ◽

Virus Strains

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Tick-borne encephalitides

10.1093/med/9780198570028.003.0044 ◽

2011 ◽

Author(s):

Patricia A. Nuttall

Keyword(s):

North America ◽

Tick Species ◽

Encephalitis Virus ◽

Virus Family ◽

Wild Mammals ◽

Tick Borne Encephalitis ◽

Powassan Virus ◽

Louping Ill ◽

Tick Borne Encephalitis Virus ◽

Far Eastern

Tick-borne encephalitides are caused by three different viruses transmitted by ticks and belonging to the Flaviviridae virus family: tick-borne encephalitis virus (Far Eastern, Siberian, and European subtypes), louping ill virus, and Powassan virus (including deer tick virus). These viruses cause encephalitis affecting humans in Eurasia and North America. In nature, they are maintained in transmission cycles involving Ixodes tick species and small or medium-sized wild mammals. The tick-borne flavivirus group is one of the most intensely studied groups of tick-borne pathogens.

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Effect of Glycosaminoglycans on Pathogenic Properties Far-Eastern Tick-Borne Encephalitis Virus

Bulletin of Experimental Biology and Medicine ◽

10.1007/s10517-019-04555-4 ◽

2019 ◽

Vol 167 (4) ◽

pp. 482-485 ◽

Cited By ~ 1

Author(s):

G. N. Leonova ◽

S. I. Belikov

Keyword(s):

Encephalitis Virus ◽

Tick Borne Encephalitis ◽

Tick Borne Encephalitis Virus ◽

Far Eastern

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Evaluation of European tick-borne encephalitis virus vaccine against recent Siberian and far-eastern subtype strains

Vaccine ◽

10.1016/s0264-410x(01)00218-3 ◽

2001 ◽

Vol 19 (32) ◽

pp. 4774-4779 ◽

Cited By ~ 35

Author(s):

Daisuke Hayasaka ◽

Akiko Goto ◽

Kentarou Yoshii ◽

Tetsuya Mizutani ◽

Hiroaki Kariwa ◽

...

Keyword(s):

Virus Vaccine ◽

Encephalitis Virus ◽

Tick Borne Encephalitis ◽

Tick Borne Encephalitis Virus ◽

Far Eastern

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Comparative analysis of genomes of tick-borne encephalitis virus strains isolated from mosquitoes and ticks

Voprosy Virusologii ◽

10.18821/0507-4088-2017-62-1-30-35 ◽

2017 ◽

Vol 62 (1) ◽

pp. 30-35 ◽

Cited By ~ 1

Author(s):

N. M. Pukhovskaya ◽

O. V. Morozova ◽

N. B. Belozerova ◽

S. V. Bakhmetyeva ◽

N. P. Vysochina ◽

...

Keyword(s):

Vaccine Strain ◽

Far East ◽

Encephalitis Virus ◽

Ixodes Persulcatus ◽

Aedes Vexans ◽

Tick Borne Encephalitis ◽

Tbev Strain ◽

Natural Foci ◽

Tick Borne Encephalitis Virus ◽

Far Eastern

The tick-borne encephalitis virus (TBEV) strain Lazo MP36 was isolated from the pool of mosquitoes Aedes vexans collected in Lazo region of Khabarovsk territory in August 2014. Phylogenetic analysis of the strain Lazo MP36 complete genome (GenBank accession number KT001073) revealed its correspondence to the TBEV Far Eastern subtype and differences from the following strains: 1) from ticks Ixodes persulcatus P. Schulze, 1930 [vaccine strain 205 (JX498939) and strains Khekhtzir 1230 (KF880805), Chichagovka (KP844724), Birobidzhan 1354 (KF880805) isolated in 2012-2013]; 2) from mosquitoes [strain Malyshevo (KJ744034) isolated in 1978 from Aedes vexans nipponii in Khabarovsk territory; strain Sakhalin 6-11 isolated from the pool of mosquitoes in 2011 (KF826916)]; 3) from human brain [vaccine strain Sofjin (JN229223), Glubinnoe/2004(DQ862460). Kavalerovo (DQ862460), Svetlogorie (DQ862460)]. The fusion peptide necessary for flavivirus entry to cells of the three TBEV strains isolated from mosquitoes (Lazo MP36, Malyshevo and Sakhalin 6-11) has the canonical structure 98-DRGWGNHCGLFGKGSI-113 for the tick-borne flaviviruses. Amino acid transition H104G typical for the mosquito-borne flaviviruses was not found. Structures of 5’- and 3’-untranslated (UTR) regions of the TBEV strains from mosquitoes were 85-98% homologous to the TBEV strains of all subtypes without recombination with mosquito-borne flaviviruses found in the Far East of Russia. Secondary structures of 5’- and 3'-UTR as well as cyclization sequences (CS) of types a and B are highly homologous for all TBEV isolates independently of the biological hosts and vectors. similarity of the genomes of the TBEV isolates from mosquitoes, ticks and patients as well as pathogenicity of the isolates for new-borne laboratory mice and tissue cultures might suggest a possible role of mosquitoes in the TBEV circulation in natural foci as an accidental or additional virus carrier.

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