Delimitation of the Tick-Borne Flaviviruses. Resolving the Tick-Borne Encephalitis virus and Louping-Ill Virus Paraphyletic Taxa

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.

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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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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 ◽

Tick Borne Encephalitis Virus ◽

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.

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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.

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Tick-Borne Encephalitis Virus and Louping-Ill Virus May Co-Circulate in Southern Norway

Vector-Borne and Zoonotic Diseases ◽

10.1089/vbz.2012.1023 ◽

2013 ◽

Vol 13 (10) ◽

pp. 762-768 ◽

Cited By ~ 19

Author(s):

Bjørnar Ytrehus ◽

Kirsti Vainio ◽

Susanne G. Dudman ◽

Janice Gilray ◽

Kim Willoughby

Keyword(s):

Encephalitis Virus ◽

Tick Borne Encephalitis ◽

Louping Ill ◽

Tick Borne Encephalitis Virus ◽

Southern Norway

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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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