scholarly journals Rate of evolution and molecular epidemiology of tick-borne encephalitis virus in Europe, including two isolations from the same focus 44 years apart

2012 ◽  
Vol 93 (4) ◽  
pp. 786-796 ◽  
Author(s):  
Nathalie Y. Uzcátegui ◽  
Tarja Sironen ◽  
Irina Golovljova ◽  
Anu E. Jääskeläinen ◽  
Hannamari Välimaa ◽  
...  

Tick-borne encephalitis virus (TBEV) is a member of the family Flaviviridae. It is transmitted by Ixodes spp. ticks in a cycle involving rodents and small mammals. TBEV has three subtypes: European, Siberian and Far Eastern. The virus causes thousands of cases of meningoencephalitis in Europe annually, with an increasing trend. The increase may be attributed to a complex network of elements, including climatic, environmental and socio-economic factors. In an attempt to understand the evolutionary history and dispersal of TBEV, to existing genetic data we add two novel complete ORF sequences of TBEV strains from northern Europe and the completion of the genome of four others. Moreover, we provide a unique measure for the natural rate of evolution of TBEV by studying two isolations from the same forest on an island in Åland archipelago 44 years apart. For all isolates, we analysed the phylogeny, rate of evolution and probable time of radiation of the different TBEV strains. The results show that the two lineages of TBEV in different Ixodes species have evolved independently for approximately 3300 years. Notably, rapid radiation of TBEV-Eur occurred approximately 300 years ago, without the large-scale geographical clustering observed previously for the Siberian subtype. The measurements from the natural rate of evolution correlated with the estimates done by phylogenetic programs, demonstrating their robustness.

2018 ◽  
Vol 39 (4) ◽  
pp. 191 ◽  
Author(s):  
Gerhard Dobler

Tick-borne encephalitis (TBE) is the most important tick-transmitted human viral disease in Europe and Asia with up to 10000 human cases annually. The etiologic agents of TBE are the three subtypes of tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus in the family Flaviviridae. The Far-Eastern subtype and the Siberian subtype are both mainly transmitted by Ixodes persulcatus; the European subtype is mainly transmitted by Ixodes ricinus. Besides tick bite, TBEV can be transmitted by unpasteurised milk from goat, sheep and cattle during the viremic phase of infection by the oral route of infection (alimentary form of TBE). There is no treatment for TBE available, but there are effective and well tolerated vaccines against TBE, which are recommended for people living or travelling to endemic countries with a risk of infection.


Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1494
Author(s):  
Ivan K. Baykov ◽  
Pavel Y. Desyukevich ◽  
Ekaterina E. Mikhaylova ◽  
Olga M. Kurchenko ◽  
Nina V. Tikunova

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.


Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 451 ◽  
Author(s):  
Mareike Kubinski ◽  
Jana Beicht ◽  
Thomas Gerlach ◽  
Asisa Volz ◽  
Gerd Sutter ◽  
...  

Tick-borne encephalitis virus (TBEV), a member of the family Flaviviridae, is one of the most important tick-transmitted viruses in Europe and Asia. Being a neurotropic virus, TBEV causes infection of the central nervous system, leading to various (permanent) neurological disorders summarized as tick-borne encephalitis (TBE). The incidence of TBE cases has increased due to the expansion of TBEV and its vectors. Since antiviral treatment is lacking, vaccination against TBEV is the most important protective measure. However, vaccination coverage is relatively low and immunogenicity of the currently available vaccines is limited, which may account for the vaccine failures that are observed. Understanding the TBEV-specific correlates of protection is of pivotal importance for developing novel and improved TBEV vaccines. For affording robust protection against infection and development of TBE, vaccines should induce both humoral and cellular immunity. In this review, the adaptive immunity induced upon TBEV infection and vaccination as well as novel approaches to produce improved TBEV vaccines are discussed.


Author(s):  
Patricia A. Nuttall

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.


2019 ◽  
Vol 93 (8) ◽  
Author(s):  
Xu Yang ◽  
Jianxun Qi ◽  
Ruchao Peng ◽  
Lianpan Dai ◽  
Ernest A. Gould ◽  
...  

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.


Vaccine ◽  
2001 ◽  
Vol 19 (32) ◽  
pp. 4774-4779 ◽  
Author(s):  
Daisuke Hayasaka ◽  
Akiko Goto ◽  
Kentarou Yoshii ◽  
Tetsuya Mizutani ◽  
Hiroaki Kariwa ◽  
...  

2017 ◽  
Vol 62 (1) ◽  
pp. 30-35 ◽  
Author(s):  
N. M. Pukhovskaya ◽  
O. V. Morozova ◽  
N. B. Belozerova ◽  
S. V. Bakhmetyeva ◽  
N. P. Vysochina ◽  
...  

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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