Dominance of temperature-sensitive phenotypes. I. Studies of the mechanism of inhibition of the growth of wild-type vesicular stomatitis virus.

It has been reported previously that temperature-sensitive (ts) mutants of vesicular stomatitis virus (VSV) with an RNA- phenotype interfere with the growth of wild-type (wt)-VSV at both the permissive (34 degrees) and nonpermissive (39.5 degrees) temperatures (J. S. Youngner and D. O. Quagliana (1976) J. Virol. 19, 102-107). Investigation of the mechanism of this interference has revealed the following information. In double infection with RNA- ts mutants and wt-VSV, the cumulative synthesis of viral RNA is inhibited. By varying the relative multiplicities of the two viruses, it was observed that the level of RNA synthesis reflects the level of interference with wt-VSV growth. Although viral RNA synthesis was severely compromised in double infections, this inhibition was not at the level of primary transcription or the translation of primary transcripts. Rather, secondary transcription and genome RNA replication were drastically reduced. Sequential infection with wt-VSV and the ts mutants revealed that there is an early point in the replication cycle of wt-VSV (1 to 2 hr) after which the ts mutants can no longer interfere with the growth of wt-VSV. Ultraviolet irradiation of ts G 41, a mutant belonging to complementation group IV, was used to determine the target size of the interference function. The calculated value for the target size was very close to the target size of the N gene. Additional experiments showed that RNA+ ts mutants representing complementation groups III and V also were able to interfere with the growth of wt-VSV.