title: Microevolution of tick-borne encephalitis virus in course of host alternation.
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.
authors.affiliation: M.P. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow Region 142782, Russia.
authors.forename: Lidiya Iu
authors.initials: LIu
authors.lastname: Romanova
authors.forename: Anatoly P
authors.initials: AP
authors.lastname: Gmyl
authors.forename: Tatiana I
authors.initials: TI
authors.lastname: Dzhivanian
authors.forename: Denis V
authors.initials: DV
authors.lastname: Bakhmutov
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Lukashev
authors.forename: Larissa V
authors.initials: LV
authors.lastname: Gmyl
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Rumyantsev
authors.forename: Ludmila A
authors.initials: LA
authors.lastname: Burenkova
authors.forename: Vasilii A
authors.initials: VA
authors.lastname: Lashkevich
authors.forename: Galina G
authors.initials: GG
authors.lastname: Karganova
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002490:Central Nervous System / Q000821:virology; D004669:Encephalitis Viruses, Tick-Borne / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D004675:Encephalitis, Tick-Borne / Q000821:virology*; D019143:Evolution, Molecular; D016679:Genome, Viral / Q000235:genetics; D026863:Ixodidae; D051379:Mice; D008969:Molecular Sequence Data; D013552:Swine; D010948:Viral Plaque Assay; D014774:Virulence / Q000235:genetics*; D014779:Virus Replication
chemical_list: D020121:5' Untranslated Regions