[Genomic sequence of hepatitis A virus L-A-1 vaccine strain].
OBJECTIVE
To study the genome sequence of hepatitis A virus L-A-1 strain which has been applied for live attenuated vaccine production in China, to compare with other HAV strains, to understand some characteristics of L-A-1 strain, and to find the mechanism of attenuation and cell adaptation.


METHODS
Genome fragments were prepared by antigen-capture PCR from infected cell (2BS), PCR products were cloned into T vector, sequenced and analyzed by using bioinformatics program.


RESULTS
Analysis of the genomic sequences(nt 25-7,418) showed that the open reading frame contains 6,675 nucleotides in length encoding 2,225 amino acids. Sequence homology comparison showed 98.00% and 94.00% homology at nucleotide level, and 98.51% and 98.65% homology at amino acid level with international strains MBB and HM 175, respectively. Through comparison with other attenuated, cell adapted and cytopathic effect (CPE) strains, L-A-1 strain had mutation at nt 152, 591, 646, 687 and insertion at nt 180-181 in 5?NTR and had mutation at nt 3,889 (aa 1 052-Val) in 2B region, these mutations and insertion are molecular basis for cell adaptation; mutation at nt 4,185 (aa 1 152-Lys) in 2C region should be attenuated marker; deletion in 3A region (nt 5,020-5,025) that caused two amino acids deletion is virus fast growth basis.


CONCLUSIONS
Through analyzing L-A-1 strain genomic sequence, certain sites related to cell adaptation and attenuation were found.
Jiang
Chun-lai
CL
Changchun Institute of Biological Products, Changchun 130062, China.
Wang
Peng-fu
PF
Liu
Jing-ye
JY
Zhang
Hua-yuan
HY
Wan
Zong-ju
ZJ
D000220:Adaptation, Biological / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D017353:Gene Deletion; D016679:Genome, Viral; D022362:Hepatitis A Vaccines / Q000235:genetics*; D030041:Hepatitis A virus / Q000235:genetics* / Q000254:growth & development; D009154:Mutation; D016366:Open Reading Frames / Q000235:genetics*; D017385:Sequence Homology; D014613:Vaccines, Attenuated / Q000235:genetics
D022362:Hepatitis A Vaccines; D014613:Vaccines, Attenuated