Microevolution of tick-borne encephalitis virus in course of host alternation

• Published in: Virology (New York, N.Y.) Vol. 362; no. 1; pp. 75 - 84
• Main Authors: Romanova, Lidiya Iu, Gmyl, Anatoly P, Dzhivanian, Tatiana I, Bakhmutov, Denis V, Lukashev, Alexander N, Gmyl, Larissa V, Rumyantsev, Alexander A, Burenkova, Ludmila A, Lashkevich, Vasilii A, Karganova, Galina G
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25-05-2007
• Subjects: 5' Untranslated Regions - genetics; Amino Acid Substitution - genetics; Animals; Cell Line; Central Nervous System - virology; Encephalitis Viruses, Tick-Borne - genetics; Encephalitis Viruses, Tick-Borne - pathogenicity; Encephalitis Viruses, Tick-Borne - physiology; Encephalitis, Tick-Borne - virology; evolution; Evolution, Molecular; Flavivirus; GAG-binding phenotype; genetic variation; Genome, Viral - genetics; glycoproteins; Host alternation; Infectious Disease; Ixodidae; Mice; Microevolution; Molecular Sequence Data; Neuroinvasiveness; phenotypic variation; sequence analysis; Swine; Tick-borne encephalitis virus; Viral Plaque Assay; viral proteins; Virulence - genetics; Virus Replication; Neuroinvasiveness; Microevolution; Tick-borne encephalitis virus; Flavivirus; GAG-binding phenotype; Host alternation
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2006.12.013

Abstract Two tick-borne encephalitis (TBE) virus variants were studied: mouse brain-adapted strain EK-328 and its derivate adapted to Hyalomma marginatum ticks. The tick-adapted virus exhibited small-plaque phenotype and slower replication in PEK cells, higher yield in ticks, decreased neuroinvasiveness in mice, increased binding to heparin-sepharose. A total of 15 nucleotide substitutions distinguished genomes of these variants, six substitutions resulted in protein sequence alterations, and two were in 5′NTR. Two amino acid substitutions in E protein were responsible for the observed phenotypic differences. Data obtained during reverse passaging of the tick-adapted virus in vivo and in vitro suggest that TBE virus exists as a heterogeneous population that contains virus variants most adapted to reproduction in either ticks or mammals. Host switch results in a change in the ratio of these variants in the population. Plaque purification of the tick-adapted virus resulted in the prompt emergence of new mutants with different virulence for mammals.