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

Beena Puri*, William M. Nelson, Erik A. Henchal, Charles H. Hoke, Kenneth H. Eckels, Doria R. Dubois, Kevin R. Porter, Curtis G. Hayes

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


The complete nucleotide sequences of the genomes of dengue-1 virus virulent 45AZ5 PDK-0 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-0 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-0, 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-0 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-0 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-0 and 27.

Original languageEnglish
Pages (from-to)2287-2291
Number of pages5
JournalJournal of General Virology
Issue number9
StatePublished - Sep 1997
Externally publishedYes


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