A BHK-21 cell culture-adapted tick-borne encephalitis virus mutant is attenuated for neuroinvasiveness.
We derived the baby hamster kidney (BHK)-21 cell culture-adapted, tick-borne encephalitis (TBE) virus mutant. To reveal the pathogenicity of the TBE virus, we compared the pathogenicity of the mutant (Oshima Cl-1) and parental (Oshima 5-10) virus in mouse model. The neurovirulence of mutant in mice was identical to that of parent. However, the level of neuroinvasiveness was higher for parent than for mutant. The degrees of viremia and virus titers in the spleen were lower in mice that were inoculated subcutaneously (s.c.) with mutant than in mice that received parent. Unlike parent, mutant was rarely detected in the brains of s.c. inoculated mice. Genetic analysis revealed that mutant had single amino acid substitutions in each of the E and NS5 proteins compared with parent. Furthermore, while mutant infection of BHK-21 cells was inhibited by glycosaminoglycans (GAGs), this was not the case for parent. In summary, the BHK-21-cell-adapted mutant virus showed reduced neuroinvasiveness in mice due to low-level induction of viremia. The attenuation process involved a single amino acid change in the E protein, which may have resulted in the rapid clearance of the virus due to its high affinity for negatively charged molecules in vivo.
Goto
Akiko
A
Laboratory of Public Health, Graduate School of Veterinary Medicine, Hokkaido University, Kita-18 Nishi-9, Kita-ku, Sapporo 060-0818, Japan.
Hayasaka
Daisuke
D
Yoshii
Kentarou
K
Mizutani
Tetsuya
T
Kariwa
Hiroaki
H
Takashima
Ikuo
I
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis; D001921:Brain / Q000473:pathology / Q000821:virology*; D002460:Cell Line; D006224:Cricetinae; D004669:Encephalitis Viruses, Tick-Borne / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity*; D004675:Encephalitis, Tick-Borne / Q000473:pathology / Q000517:prevention & control* / Q000821:virology*; D015683:Gene Products, gag / Q000096:biosynthesis; D016679:Genome, Viral; D006386:Hemagglutination Tests; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics / Q000276:immunology; D009500:Neutralization Tests; D013154:Spleen / Q000821:virology; D014613:Vaccines, Attenuated / Q000276:immunology; D010948:Viral Plaque Assay; D014765:Viral Vaccines / Q000276:immunology*; D014766:Viremia / Q000097:blood; D014779:Virus Replication
D000914:Antibodies, Viral; D015683:Gene Products, gag; D014613:Vaccines, Attenuated; D014765:Viral Vaccines