INHIBITION OF SENDAI VIRUS GENOME REPLICATION DUE TO PROMOTER-INCREASED SELECTIVITY - A POSSIBLE ROLE FOR THE ACCESSORY C-PROTEIN

The role of the negative-stranded virus accessory C proteins is diffic ult to assess because they appear sometimes as nonessential and thereb y of no function. On the other hand, when a function is found, as in t he case of Sendai virus, it represents an enigma, in that the C protei ns inhibit replication under conditions where the infection follows an exponential course. Furthermore, this inhibitory function is exerted differentially: in contrast to the replication of internal deletion de fective interfering (DI) RNAs, that of copy-back DI RNAs appears to es cape inhibition, under certain experimental conditions (in vivo assay) . In a reexamination of the C effect by the reverse genetics approach, it was found that copy-back RNA replication is inhibited by C in vivo as well, under conditions where the ratio of C to copy-back template is increased, This effect can be reversed by an increase in P but not L protein. The ''rule of six'' was differentially observed in the pres ence or absence of C. Finally, a difference in the ability of the repl icating complex to tolerate promoter modifications in RNA synthesis in itiation was shown to occur in the presence or the absence of C as wel l, We propose that C acts by increasing the selectivity of the replica ting complex for the promoter cis-acting elements governing its activi ty. The inhibitory effect of C becomes the price to pay for this incre ased selectivity.