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Published on: December 29, 2015
Pathologic potential of variant clones of the oshima strain of far-eastern subtype tick-borne encephalitis virus
Le Xuan Luat1, Mya Myat Ngwe Tun1, Corazon C Buerano1
1Department of Virology, Institute of Tropical Medicine, Nagasaki University.
Abstract:
Tick-borne encephalitis virus (TBEV) is a zoonotic agent that causes acute central nervous system (CNS) disease in humans. We previously suggested that immune response in addition to CNS infection contribute to mouse mortality following TBEV infection. However, we did not examine the influence of virus variants in the previous study. Therefore, in this study, we investigated the biological and pathologic potentials of the variant clones in the TBEV Oshima strain. We isolated eight variant clones from the stock virus of the Oshima 5-10. These variants exhibited different plaque morphologies in BHK cells and pathogenic potentials in mice. Full sequences of viral genomes revealed that each of the variant clones except one had specific combinations of nucleotide and amino acid changes at certain positions different from the parent strain. We also showed that an amino acid substitution of Glu122→Gly in the E protein could have affected virus infection and replication in vivo, as well as the attenuated pathogenicity in mice. These data confirm the presence of virus variants or quasispecies from the parent strain. Further elucidation of the effect of each variant clone on immune responses such as the T-cell response is an important priority in the development of an effective vaccine and treatment strategies for tick-borne encephalitis.
Insights
Tick-borne encephalitis virus (TBEV) variants were isolated and studied. An E protein substitution influenced TBEV
Area of Science:
- Virology
- Immunology
- Pathology
Background:
- Tick-borne encephalitis virus (TBEV) causes severe central nervous system (CNS) disease.
- Previous research suggested TBEV infection and immune response contribute to mortality.
- The role of TBEV variants in pathogenicity was not previously examined.
Purpose of the Study:
- To investigate the biological and pathological potential of TBEV variant clones from the Oshima strain.
- To identify genetic differences contributing to variant characteristics.
- To understand the impact of specific mutations on TBEV pathogenicity.
Main Methods:
- Isolation and characterization of eight TBEV variant clones from the Oshima 5-10 strain.
- Assessment of plaque morphology in BHK cells and pathogenicity in mice.
- Full genome sequencing of viral variants to identify genetic alterations.
Main Results:
- Isolated TBEV variants displayed distinct plaque morphologies and pathogenic potentials in mice.
- Genetic analysis revealed specific nucleotide and amino acid changes in most variants compared to the parent strain.
- An E protein substitution (Glu122→Gly) was associated with altered in vivo infection, replication, and reduced mouse pathogenicity.
Conclusions:
- The TBEV Oshima strain harbors diverse variants (quasispecies).
- Specific genetic mutations, like the E protein substitution, significantly impact TBEV's biological behavior and virulence.
- Understanding variant-specific immune responses is crucial for developing effective TBEV vaccines and treatments.
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