BIOCHEMICAL CHARACTERIZATIONS OF 2 TEMPERATURE-SENSITIVE AND ATTENUATED STRAINS OF RESPIRATORY SYNCYTIAL VIRUS SUBGROUP-B

Cold-adapted, temperature-sensitive (ts), attenuated strains of respir atory syncytial virus have been developed from a B subgroup clinical i solate for potential use as vaccine candidates, The replication of two B subgroup ts mutant viruses (2B33F and 2B20L) at the permissive and nonpermissive temperatures have been compared with that of the parenta l 2B virus to establish differences that may account for their ts and/ or attenuated phenotypes. We have shown that the fs restriction at 39 degrees C in the replication of the two mutant viruses in tissue cultu re occurs at a step after virus adsorption but before or including ini tiation of virus specific mRNA transcription, At the permissive temper ature of 32 degrees C a 12- to 24-h delay in the accumulation of mRNA for both mutant viruses in comparison to that of the parental 2B virus was exhibited, This effect was mirrored by equivalent delays in viral protein synthesis and production of infectious virus, By 36 h postinf ection both mutants had produced levels of viral mRNA, protein, and in fectious virus that were similar to those of the parent virus at 32 de grees C, ts+ revertant viruses derived from both mutants have also rev erted in their viral mRNA, protein, and infectious virus production ki netics at 32 degrees C to rates more like those exhibited by the paren tal 2B virus. This suggests a positive correlation between the ts. ste p in the replication of the mutant viruses and the initial delay in mR NA production that occurs at the permissive temperature.