Mutations in the NS2B and NS3 genes affect mouse neuroinvasiveness of a Western European field strain of tick-borne encephalitis virus.
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.
Růzek
Daniel
D
Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic, Branisovská 31, CZ-370 05 Ceské Budejovice, Czech Republic. ruzekd@paru.cas.cz
Gritsun
Tamara S
TS
Forrester
Naomi L
NL
Gould
Ernest A
EA
Kopecký
Jan
J
Golovchenko
Maryna
M
Rudenko
Nataliia
N
Grubhoffer
Libor
L
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000833:Animals, Suckling; D001483:Base Sequence; D001921:Brain / Q000821:virology*; D004669:Encephalitis Viruses, Tick-Borne / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D004675:Encephalitis, Tick-Borne / Q000401:mortality / Q000503:physiopathology* / Q000821:virology; D005060:Europe; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D008958:Models, Molecular; D009154:Mutation; D020365:RNA Helicases / Q000737:chemistry / Q000235:genetics; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D012692:Serial Passage; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics; D013987:Ticks / Q000821:virology; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics*; D014774:Virulence; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D020365:RNA Helicases; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; C080102:NS2B protein, flavivirus; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases