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GAG-binding variants of tick-borne encephalitis virus
L I Kozlovskaya1, D I Osolodkin, A S Shevtsova
1Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow Region 142782, Russia.
Virology
|January 13, 2010
Summary
This study identifies glycosaminoglycan-binding tick-borne encephalitis virus (TBEV) variants in nature. These variants exhibit specific traits, including low neuroinvasiveness, linked to E protein mutations and flexibility.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Flaviviruses can develop mutations affecting glycosaminoglycan (GAG) binding and neuroinvasiveness.
- Previous studies focused on laboratory-generated flavivirus mutants.
Purpose of the Study:
- To investigate the presence and characteristics of GAG-binding tick-borne encephalitis virus (TBEV) variants within natural populations.
- To understand the molecular basis and phenotypic consequences of GAG-binding in TBEV.
Main Methods:
- Analysis of TBEV isolates.
- Heparin-Sepharose chromatography to assess GAG-binding affinity.
- Phenotypic characterization (plaque size, hemagglutination).
- Molecular modeling and dynamics simulations of the E protein.
Main Results:
- Naturally occurring GAG-binding TBEV variants were identified.
- These variants displayed a small plaque phenotype, lacked hemagglutination at pH 6.4, and showed low neuroinvasiveness in mice.
- Mutations increasing the E protein's charge were necessary but not sufficient for GAG-binding.
- E protein flexibility influences the phenotypic expression of charge-increasing substitutions.
Conclusions:
- GAG-binding variants of TBEV exist in natural viral populations.
- The GAG-binding phenotype is associated with specific, attenuated viral characteristics.
- Viral E protein flexibility plays a crucial role in the manifestation of GAG-binding properties.
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