PMID- 12922141
OWN - NLM
STAT- MEDLINE
DCOM- 20040325
LR  - 20190728
IS  - 0264-410X (Print)
IS  - 0264-410X (Linking)
VI  - 21
IP  - 25-26
DP  - 2003 Sep 8
TI  - A BHK-21 cell culture-adapted tick-borne encephalitis virus mutant is attenuated 
      for neuroinvasiveness.
PG  - 4043-51
AB  - 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.
FAU - Goto, Akiko
AU  - Goto A
AD  - Laboratory of Public Health, Graduate School of Veterinary Medicine, Hokkaido 
      University, Kita-18 Nishi-9, Kita-ku, Sapporo 060-0818, Japan.
FAU - Hayasaka, Daisuke
AU  - Hayasaka D
FAU - Yoshii, Kentarou
AU  - Yoshii K
FAU - Mizutani, Tetsuya
AU  - Mizutani T
FAU - Kariwa, Hiroaki
AU  - Kariwa H
FAU - Takashima, Ikuo
AU  - Takashima I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Antibodies, Viral)
RN  - 0 (Gene Products, gag)
RN  - 0 (Vaccines, Attenuated)
RN  - 0 (Viral Vaccines)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibodies, Viral/analysis/biosynthesis
MH  - Brain/pathology/*virology
MH  - Cell Line
MH  - Cricetinae
MH  - Encephalitis Viruses, Tick-Borne/*genetics/immunology/*pathogenicity
MH  - Encephalitis, Tick-Borne/pathology/*prevention & control/*virology
MH  - Gene Products, gag/biosynthesis
MH  - Genome, Viral
MH  - Hemagglutination Tests
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Molecular Sequence Data
MH  - Mutation/genetics/immunology
MH  - Neutralization Tests
MH  - Spleen/virology
MH  - Vaccines, Attenuated/immunology
MH  - Viral Plaque Assay
MH  - Viral Vaccines/*immunology
MH  - Viremia/blood
MH  - Virus Replication
EDAT- 2003/08/19 05:00
MHDA- 2004/03/26 05:00
CRDT- 2003/08/19 05:00
PHST- 2003/08/19 05:00 [pubmed]
PHST- 2004/03/26 05:00 [medline]
PHST- 2003/08/19 05:00 [entrez]
AID - S0264410X0300269X [pii]
AID - 10.1016/s0264-410x(03)00269-x [doi]
PST - ppublish
SO  - Vaccine. 2003 Sep 8;21(25-26):4043-51. doi: 10.1016/s0264-410x(03)00269-x.