GAG-binding variants of tick-borne encephalitis virus.

L I Kozlovskaya, D I Osolodkin, A S Shevtsova, L Iu Romanova, Y V Rogova, T I Dzhivanian, V N Lyapustin, G P Pivanova, A P Gmyl, V A Palyulin, G G Karganova

Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow Region 142782, Russia.

Virology 2010 Mar 15

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Previously different authors described various flavivirus mutants with high affinity to cell glycosaminoglycans and low neuroinvasiveness in mice that were obtained consequently passages in cell cultures or in ticks. In present study the analysis of TBEV isolates has shown existence of GAG-binding variants in natural virus population. Affinity to GAG has been evaluated by sorption on heparin-Sepharose. GAG-binding phenotype corresponds to such virus properties, like small plaque phenotype in PEK cells, absence of hemagglutination at pH 6.4, and low neuroinvasiveness in mice. Mutations increasing charge of E protein were necessary but not sufficient for acquisition of GAG-binding phenotype. Molecular modeling and molecular dynamics simulation have shown that the flexibility of E protein molecule could bear influence on the phenotypic manifestation of substitutions increasing charge of the virions. Copyright 2009 Elsevier Inc. All rights reserved.

Citation

L I Kozlovskaya, D I Osolodkin, A S Shevtsova, L Iu Romanova, Y V Rogova, T I Dzhivanian, V N Lyapustin, G P Pivanova, A P Gmyl, V A Palyulin, G G Karganova. GAG-binding variants of tick-borne encephalitis virus. Virology. 2010 Mar 15;398(2):262-72