Inhibition of Sendai virus genome replication due to promoter-increased selectivity: a possible role for the accessory C proteins.
The role of the negative-stranded virus accessory C proteins is difficult to assess because they appear sometimes as nonessential and thereby of no function. On the other hand, when a function is found, as in the case of Sendai virus, it represents an enigma, in that the C proteins 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 defective interfering (DI) RNAs, that of copy-back DI RNAs appears to escape 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 presence or absence of C. Finally, a difference in the ability of the replicating complex to tolerate promoter modifications in RNA synthesis initiation was shown to occur in the presence or the absence of C as well. We propose that C acts by increasing the selectivity of the replicating complex for the promoter cis-acting elements governing its activity. The inhibitory effect of C becomes the price to pay for this increased selectivity.
Tapparel
C
C
Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland.
Hausmann
S
S
Pelet
T
T
Curran
J
J
Kolakofsky
D
D
Roux
L
L
D012321:DNA-Directed RNA Polymerases; D003673:Defective Viruses / Q000235:genetics / Q000502:physiology; D016679:Genome, Viral; D006367:HeLa Cells; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012367:RNA, Viral / Q000096:biosynthesis*; D018108:Respirovirus / Q000235:genetics* / Q000502:physiology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
C055859:P protein, Sendai virus; D010750:Phosphoproteins; D012367:RNA, Viral; D014764:Viral Proteins; C051221:nonstructural C protein, Sendai virus; C064365:L protein, Sendai virus; D012321:DNA-Directed RNA Polymerases