Protease and helicase domains are related to the temperature sensitivity of wild-type rubella viruses

Abstract

Wild-type rubella viruses grow well at 39°C (non-temperature sensitivity: non-ts), while vaccine strains do not (temperature sensitivity: ts). Histidine at position 1042 of the p150 region of the KRT vaccine strain was found to be responsible for ts, while wild-type viruses had tyrosine at position 1042 (Vaccine 27; 234–42, 2009). The point-mutated virus (Y1042H) based on the wild-type unexpectedly showed little reduction in growth at 39°C. In this report, several recombinant viruses were characterized, and point-mutated Y1042H together with the p90 region of KRT significantly reduced virus growth, compared to the parental wild-type virus. There was one amino acid difference at position 1497 of the helicase domain in the p90 region. Double mutation involving both positions 1042 and 1497 markedly reduced virus growth at 39°C, but single substitution at 1497 did not. The other vaccine strain (TO-336vac) was investigated, and serine at position 1159 of the protease domain in p150 was a crucial amino acid for ts and non-ts characteristics among four amino acid substitutions between TO-336vac and the wild-type. Our results suggest that protease and helicase domains in non-structural protein were consistent with ts phenotype, possibly related to the attenuation process of wild-type viruses.