TABLE 1.
Genotypes of recombinant DEN-2 16681/PDK-53 viruses
| Clone-derived virus (cognate)b | DEN-2 16681 virus determinants in PDK-53 virus backgrounda
|
DEN-2 PDK-53 determinants in 16681 backgroundc
|
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 5′NC-57 | prM-29 | NS1-53 | NS2A-181 | NS3-250 | NS4A-75 | 5′NC-57 | prM-29 | NS1-53 | NS2A-181 | NS3-250 | NS4A-75 | |
| DEN-2 PDK-53 | t | V | D | F | V | A | ||||||
| VV45R (V513) | · | · | · | · | · | · | ||||||
| P5 (V13) | c | · | · | · | · | · | ||||||
| P1 (V53) | · | · | G | · | · | · | ||||||
| P3 (V51) | · | · | · | · | E | · | ||||||
| P51 (V3) | c | · | G | · | · | · | ||||||
| P53 (V1) | c | · | · | · | E | · | ||||||
| P13 (V5) | · | · | G | · | E | |||||||
| P513 (30P-A) | c | · | G | · | E | · | ||||||
| DEN-2 16681 | c | D | G | L | E | G | ||||||
| 30P-A (P513) | · | · | · | · | · | · | ||||||
| V5 (P13) | t | · | · | · | · | · | ||||||
| V1 (P53) | · | · | D | · | · | · | ||||||
| V3 (P51) | · | · | · | · | V | · | ||||||
| V51 (P3) | t | · | D | · | · | · | ||||||
| V53 (P1) | t | · | · | · | V | · | ||||||
| V13 (P5) | · | · | D | · | V | · | ||||||
| V513 (VV45R) | t | · | D | · | V | · | ||||||
The genome of the candidate DEN-2 PDK-53 vaccine virus differs from that of its 16681 parent at nine nucleotide loci, including three silent mutations (not shown), a mutation at genome 5′NC-57 (lowercase letters), and five nucleotides encoding amino acid mutations (uppercase, single-letter abbreviations) at viral polypeptide positions prM-29, NS1-53, NS2A-181, NS3-250, and NS4A-75 (32). Genetic loci from the parental 16681 virus were engineered into the cDNA background of the PDK-53 virus-specific infectious clone, pD2/IC-VV45R. Dots indicate sequence identity with PDK-53 virus (NS3-250-Val variant). The candidate PDK-53 vaccine also contains a genetic variant that has Glu at NS3-250 (32).
The genotypes of wild-type DEN-2 16681 virus, its attenuated vaccine derivative, DEN-2 PDK-53 virus, infectious clone-derived VV45R (genetically equivalent to the PDK-53 NS3-250-Val variant) and 30P-A (equivalent to wild-type 16681) viruses, and recombinant 16681/PDK-53 viruses are shown. For designations of recombinant Px and Vx viruses, see Materials and Methods. P5 and V13 are cognate viruses, assuming that the PDK-53 virus-specific phenotype is determined predominantly by the 5′NC-57, NS1-53, and NS3-250 loci. Both P5 and V13 viruses contain the 5′NC-57-c, NS1-53-Asp, and NS3-250-Val loci within the genetic backgrounds of PDK-53 and 16681 viruses, respectively.
Genetic loci from PDK-53 virus were engineered into the cDNA background of the 16681 virus-specific infectious clone, pD2/IC-30P-A. Dots indicate sequence identity with 16681 virus.