The short Sendai virus leader region controls induction of programmed cell death.
The replication of nonsegmented minus-strand RNA genomes, like that of Sendai paramyxovirus (SeV), are controlled by the short leader regions present at each end of the linear genomes and antigenomes; the left and right promoters (PL and PR), respectively. Wild-type SeV is highly cytopathic in cell culture, because it induces programmed cell death (PCD). We have found that a recombinant SeV (rSeVGP42), in which the first 42 nt of le+ sequences at PL were replaced with the equivalent sequences of PR, and which produces infectious virus in amounts comparable to wild type, does not kill cells. Further, the increasing replacement of the terminal le+ sequences at PL with le- sequences led to a decreasing fraction of infected cells being apoptotic. This property (PCD-), moreover, is dominant in cells co-infected with SeVwt and rSeVGP42, and the mutant virus therefore appears to have gained a function which prevents PCD induced by SeVwt. Even though this virus has not been selected for naturally, it excludes SeVwt during co-infections of cultured cells or embryonated chicken eggs. The noncytopathic nature of cells infected or co-infected with rSeVGP42 leads automatically to stable, persistent infections. The mutation in rSeVGP42 is not in the protein coding regions of the viral genome, but in the 55-nt-long leader region which controls antigenome synthesis from genome templates. The SeV leader regions, which are expressed as short RNAs, thus appear to control the induction of PCD.
Garcin
D
D
Department of Genetics and Microbiology, University of Geneva School of Medicine, CMU, Switzerland.
Taylor
G
G
Tanebayashi
K
K
Compans
R
R
Kolakofsky
D
D
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002874:Chromosome Mapping; D006224:Cricetinae; D003588:Cytopathogenic Effect, Viral; D016679:Genome, Viral; D006367:HeLa Cells; D006801:Humans; D012333:RNA, Messenger; D012367:RNA, Viral; D018108:Respirovirus / Q000235:genetics* / Q000502:physiology; D017735:Virus Latency; D014779:Virus Replication
D012333:RNA, Messenger; D012367:RNA, Viral