Molecular analysis of dengue virus attenuation after serial passage in primary dog kidney cells

J Gen Virol. 1997 Sep:78 ( Pt 9):2287-91. doi: 10.1099/0022-1317-78-9-2287.

Abstract

The complete nucleotide sequences of the genomes of dengue-1 virus virulent 45AZ5 PDK-O and attenuated vaccine candidate strain 45AZ5 PDK-27 have been determined and compared with the dengue-1 virus Western Pacific (West Pac) 74 parent strain from which 45AZ5 PDK-O was derived. Twenty-five (0.23%) nucleotide and 10 (0.29%) amino acid substitutions occurred between parent strain dengue-1 virus West Pac 74 and virulent strain 45AZ5 PDK-O, which was derived from the parent by serial passage in diploid foetal rhesus lung (FRhL-2) and mutagenized with 5-azacytidine. These substitutions were preserved in the 45AZ5 PDK-27 vaccine. 45AZ5 PDK-O and PDK-27 strains, which differ by 27 passages in primary dog kidney (PDK) cells, show 25 (0.23%) nucleotide and 11 (0.32%) amino acid divergences. These comparative studies suggest that the changes which occurred between the West Pac 74 and 45AZ5 PDK-O strains may alter the biological properties of the virus but may not be important for attenuation. Important nucleotide base changes responsible for attenuation accumulated between 45AZ5 PDK-O and 27.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Dengue Virus / genetics*
  • Dengue Virus / pathogenicity*
  • Dogs
  • Genetic Variation / genetics
  • Genome, Viral
  • Humans
  • Kidney / cytology
  • Molecular Sequence Data
  • RNA, Viral / genetics
  • Sequence Analysis, DNA
  • Sequence Analysis, RNA
  • Serial Passage
  • Vaccines, Attenuated / genetics
  • Viral Vaccines / genetics*
  • Virulence

Substances

  • RNA, Viral
  • Vaccines, Attenuated
  • Viral Vaccines

Associated data

  • GENBANK/U88535
  • GENBANK/U88536
  • GENBANK/U88537