Tick-borne encephalitides

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.

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 (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.

The serological response and long-lasting resistance against infection with louping-ill virus in sheep immunized with a highly attenuated tick-borne encephalitis virus

Epidemiology and Infection ◽

10.1017/s0022172400042170 ◽

1969 ◽

Vol 67 (4) ◽

pp. 731-738 ◽

Cited By ~ 1

Author(s):

V. Mayer ◽

D. Blaškovič ◽

E. Ernek ◽

H. Libíková

Keyword(s):

Neutralizing Antibodies ◽

Encephalitis Virus ◽

Serological Response ◽

Immune Control ◽

Summer Period ◽

Tick Borne Encephalitis ◽

Louping Ill ◽

Tick Borne Encephalitis Virus

SUMMARYThe vaccination of sheep with one dose of the monkey-and mouse-attenuated tick-borne encephalitis virus (the Hy-HK 28 ‘2’ clone) causes seroconversion from negative into positive in 85% of animals. In sheep with pre-existing virus-neutralizing antibodies and increas of their titres was observed in 81%. The antibodies persisted for at least 12 months after the vaccination and during the summer period of grazing the number of serologically positive animals even increased.The vaccinated animals, in contrast to the non-immune control sheep, developed no viraemia after challenge with the virulent louping-ill virus, performed 11 months after immunization.

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 ◽

Far Eastern ◽

Virus Strains

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 ◽

Flavivirus-induced antibody cross-reactivity

Journal of General Virology ◽

10.1099/vir.0.031641-0 ◽

2011 ◽

Vol 92 (12) ◽

pp. 2821-2829 ◽

Cited By ~ 143

Author(s):

Karen L. Mansfield ◽

Daniel L. Horton ◽

Nicholas Johnson ◽

Li Li ◽

Alan D. T. Barrett ◽

...

Keyword(s):

Yellow Fever Virus ◽

Cross Reactivity ◽

Encephalitis Virus ◽

Antigenic Relationship ◽

Tick Borne Encephalitis ◽

History Of ◽

Louping Ill ◽

Antigenic Cartography ◽

The Individual

Dengue viruses (DENV) cause countless human deaths each year, whilst West Nile virus (WNV) has re-emerged as an important human pathogen. There are currently no WNV or DENV vaccines licensed for human use, yet vaccines exist against other flaviviruses. To investigate flavivirus cross-reactivity, sera from a human cohort with a history of vaccination against tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV) and yellow fever virus (YFV) were tested for antibodies by plaque reduction neutralization test. Neutralization of louping ill virus (LIV) occurred, but no significant neutralization of Murray Valley encephalitis virus was observed. Sera from some individuals vaccinated against TBEV and JEV neutralized WNV, which was enhanced by YFV vaccination in some recipients. Similarly, some individuals neutralized DENV-2, but this was not significantly influenced by YFV vaccination. Antigenic cartography techniques were used to generate a geometric illustration of the neutralization titres of selected sera against WNV, TBEV, JEV, LIV, YFV and DENV-2. This demonstrated the individual variation in antibody responses. Most sera had detectable titres against LIV and some had titres against WNV and DENV-2. Generally, LIV titres were similar to titres against TBEV, confirming the close antigenic relationship between TBEV and LIV. JEV was also antigenically closer to TBEV than WNV, using these sera. The use of sera from individuals vaccinated against multiple pathogens is unique relative to previous applications of antigenic cartography techniques. It is evident from these data that notable differences exist between amino acid sequence identity and mapped antigenic relationships within the family Flaviviridae.

Molecular Basis of a Protective/Neutralizing Monoclonal Antibody Targeting Envelope Proteins of both Tick-Borne Encephalitis Virus and Louping Ill Virus

Journal of Virology ◽

10.1128/jvi.02132-18 ◽

2019 ◽

Vol 93 (8) ◽

Cited By ~ 2

Author(s):

Xu Yang ◽

Jianxun Qi ◽

Ruchao Peng ◽

Lianpan Dai ◽

Ernest A. Gould ◽

...

Keyword(s):

Structural Analysis ◽

Encephalitis Virus ◽

Infection Rates ◽

E Proteins ◽

E Protein ◽

Tick Borne Encephalitis ◽

The Family ◽

Lateral Ridge ◽

Louping Ill ◽

Tick Borne Encephalitis Virus

ABSTRACT Tick-borne encephalitis virus (TBEV) and louping ill virus (LIV) are members of the tick-borne flaviviruses (TBFVs) in the family Flaviviridae which cause encephalomeningitis and encephalitis in humans and other animals. Although vaccines against TBEV and LIV are available, infection rates are rising due to the low vaccination coverage. To date, no specific therapeutics have been licensed. Several neutralizing monoclonal antibodies (MAbs) show promising effectiveness in the control of TBFVs, but the underlying molecular mechanisms are yet to be characterized. Here, we determined the crystal structures of the LIV envelope (E) protein and report the comparative structural analysis of a TBFV broadly neutralizing murine MAb (MAb 4.2) in complex with either the LIV or TBEV E protein. The structures reveal that MAb 4.2 binds to the lateral ridge of domain III of the E protein (EDIII) of LIV or TBEV, an epitope also reported for other potently neutralizing MAbs against mosquito-borne flaviviruses (MBFVs), but adopts a unique binding orientation. Further structural analysis suggested that MAb 4.2 may neutralize flavivirus infection by preventing the structural rearrangement required for membrane fusion during virus entry. These findings extend our understanding of the vulnerability of TBFVs and other flaviviruses (including MBFVs) and provide an avenue for antibody-based TBFV antiviral development. IMPORTANCE Understanding the mechanism of antibody neutralization/protection against a virus is crucial for antiviral countermeasure development. Tick-borne encephalitis virus (TBEV) and louping ill virus (LIV) are tick-borne flaviviruses (TBFVs) in the family Flaviviridae. They cause encephalomeningitis and encephalitis in humans and other animals. Although vaccines for both viruses are available, infection rates are rising due to low vaccination coverage. In this study, we solved the crystal structures of the LIV envelope protein (E) and a broadly neutralizing/protective TBFV MAb, MAb 4.2, in complex with E from either TBEV or LIV. Key structural features shared by TBFV E proteins were analyzed. The structures of E-antibody complexes showed that MAb 4.2 targets the lateral ridge of both the TBEV and LIV E proteins, a vulnerable site in flaviviruses for other potent neutralizing MAbs. Thus, this site represents a promising target for TBFV antiviral development. Further, these structures provide important information for understanding TBFV antigenicity.

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 ◽

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 ◽

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.