MEASLES-VIRUS ATTENUATION ASSOCIATED WITH TRANSCRIPTIONAL IMPEDIMENT AND A FEW AMINO-ACID CHANGES IN THE POLYMERASE AND ACCESSORY PROTEINS

Measles virus (MV) isolated in B95a cells, a marmoset B-cell line, ret ains full pathogenicity for cynomolgus monkeys, while its derivative o btained by adaptation to the growth in Vero cells, a monkey kidney cel l line, loses the pathogenic potential (F. Kobune, H. Sakata, and A. S ugiura, J. Virol. 64:700-705, 1990), Here, we show with a pair of stra ins, a fresh isolate (9301B) in B95a cells and its Vero cell-adapted f orm (9301V), that the in vivo attenuation parallels the decrease of re plication and syncytium-inducing capabilities in the original B95a cel ls and that these in vitro phenotypes are attributable to impediment o f transcription, which is already obvious at the level of primary tran scription catalyzed by the virion-associated RNA polymerase. On the ot her hand, cell fusion assays detected no functional difference between the glycoproteins of the two viruses. Essentially the same transcript ional impediment with reduced syncytium induction following Vero cell adaptation was found with two other pairs of strains that had been sim ilarly prepared. Nucleotide sequence comparison between the 9301B and 9301V viruses revealed that a few (at most five) amino acid changes, w hich sporadically took place in the polymerase (L and P proteins) and/ or accessory V and C proteins, were responsible for the in vitro and i n vivo attenuation through adaptation to growth in Vero cells.