Abstract
An attenuated strain (263) of the tick-borne encephalitis virus, isolated from field ticks, was either serially subcultured, 5 times in mice, or at 40 degrees C in PS cells, producing 2 independent strains, 263-m5 and 263-TR with identical genomes; both strains exhibited increased plaque size, neuroinvasiveness and temperature-resistance. Sequencing revealed two unique amino acid substitutions, one mapping close to the catalytic site of the viral protease. These observations imply that virus adaptation from ticks to mammals occurs by selection of pre-existing virulent variants from the quasispecies population rather than by the emergence of new random mutations. The significance of these observations is discussed.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Amino Acid Substitution
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Animals
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Animals, Suckling
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Base Sequence
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Brain / virology*
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Encephalitis Viruses, Tick-Borne / genetics
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Encephalitis Viruses, Tick-Borne / isolation & purification
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Encephalitis Viruses, Tick-Borne / pathogenicity*
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Encephalitis, Tick-Borne / mortality
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Encephalitis, Tick-Borne / physiopathology*
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Encephalitis, Tick-Borne / virology
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Europe
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Female
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Mice
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Mice, Inbred ICR
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Models, Molecular
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Mutation*
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RNA Helicases / chemistry
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RNA Helicases / genetics
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Selection, Genetic
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Sequence Analysis, DNA
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Serial Passage
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Serine Endopeptidases / chemistry
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Serine Endopeptidases / genetics
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Ticks / virology
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Viral Nonstructural Proteins / chemistry
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Viral Nonstructural Proteins / genetics*
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Virulence
Substances
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NS2B protein, flavivirus
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NS3 protein, flavivirus
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Viral Nonstructural Proteins
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Serine Endopeptidases
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RNA Helicases