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

doi:10.1099/0022-1317-78-9-2287

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 journal › Article › peer-review

40 Scopus citations

Abstract

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 language	English
Pages (from-to)	2287-2291
Number of pages	5
Journal	Journal of General Virology
Volume	78
Issue number	9
DOIs	https://doi.org/10.1099/0022-1317-78-9-2287
State	Published - Sep 1997
Externally published	Yes

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title = "Molecular analysis of dengue virus attenuation after serial passage in primary dog kidney cells",

abstract = "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.",

author = "Beena Puri and Nelson, {William M.} and Henchal, {Erik A.} and Hoke, {Charles H.} and Eckels, {Kenneth H.} and Dubois, {Doria R.} and Porter, {Kevin R.} and Hayes, {Curtis G.}",

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AU - Puri, Beena

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AU - Henchal, Erik A.

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AU - Eckels, Kenneth H.

AU - Dubois, Doria R.

AU - Porter, Kevin R.

AU - Hayes, Curtis G.

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N2 - 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.

AB - 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.

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

Abstract

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