The complete nucleotide sequence of two cold-adapted, temperature-sensitive attenuated mutant vaccine viruses (cp12 and cp45) derived from the JS strain of human parainfluenza virus type 3 (PIV3).
Two cold-passaged mutant vaccine viruses (cp12 and cp45) derived from the JS wild-type (wt) strain of human parainfluenza virus type 3 (PIV3) have been sequenced. These mutant viruses display the cold-adapted (ca), temperature-sensitive (ts), and attenuation (att) phenotypes. Sequence data indicate that both cp12 and cp45 sustained nucleotide substitutions during cold passage and subsequent cloning. Fifteen nucleotide changes were present in cp12 and 18 in cp45. Of these changes, some were present in the sequence of the prototype wt strain (Wash/47885/57) or were non-coding changes present in the open reading frames (ORFs). These were considered unlikely to be of significance in contributing to phenotypic differences between the mutants and the JS wt. There were nine remaining changes in cp12 and eight in cp45 that would most likely contribute to their phenotypes. For cp12, two were non-coding changes in regulatory regions, one in the 3' genome leader and one in the NP gene transcription start signal. The remaining seven changes resulted in amino acid substitutions in NP, F, HN, and L. For cp45, two mutations were in a non-coding regulatory region, the 3' genome leader. The remaining six changes resulted in amino acid substitutions in F, HN, and L. Only one amino acid substitution was conserved between cp12 and cp45 (a valine to alanine change at position 384 of the HN gene). These results should prove useful in the future in understanding the genetic basis of attenuation of the cold-passaged PIV3 candidate vaccine viruses.
Stokes
A
A
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Tierney
E L
EL
Sarris
C M
CM
Murphy
B R
BR
Hall
S L
SL
D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D001483:Base Sequence; D003080:Cold Temperature; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010224:Parainfluenza Virus 3, Human / Q000235:genetics* / Q000502:physiology; D014613:Vaccines, Attenuated / Q000235:genetics*; D014765:Viral Vaccines / Q000235:genetics*
D014613:Vaccines, Attenuated; D014765:Viral Vaccines