title: The various Sendai virus C proteins are not functionally equivalent and exert both positive and negative effects on viral RNA accumulation during the course of infection.
abstract: Recombinant Sendai viruses were prepared which cannot express their Cprime, C, or Cprime plus C proteins due to mutation of their respective start codons ([Cprime-minus], [C-minus] and [double mutant], respectively). The [Cprime-minus] and [C-minus] stocks were similar to that of wild-type (wt) virus in virus titer and plaque formation, whereas the double-mutant stock had a much-reduced PFU or 50% egg infective dose/particle ratio and produced very small plaques. Relative to the wt virus infection, the [Cprime-minus] and [C-minus] infections of BHK cells resulted in significantly greater accumulation of viral RNAs, consistent with the known inhibitory effects of the Cprime and C proteins. The double-mutant infection, in contrast, was delayed in its accumulation of viral RNAs; however, once accumulation started, overaccumulation quickly occurred, as in the single-mutant infections. Our results suggest that the Cprime and C proteins both provide a common positive function early in infection, so that only the double mutant undergoes delayed RNA accumulation and exhibits the highly debilitated phenotype. Later in infection, the same proteins appear to act as inhibitors of RNA accumulation. In infections of mice, [Cprime-minus] was found to be as virulent as wt virus whereas [C-minus] was highly attenuated. These results suggest that the Cprime and C proteins cannot be functionally equivalent, since C can replace Cprime for virulence in mice whereas Cprime cannot replace C.
authors.affiliation: Department of Genetics and Microbiology, University of Geneva School of Medicine, CH1211 Geneva, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Latorre
authors.forename: T
authors.initials: T
authors.lastname: Cadd
authors.forename: M
authors.initials: M
authors.lastname: Itoh
authors.forename: J
authors.initials: J
authors.lastname: Curran
authors.forename: D
authors.initials: D
authors.lastname: Kolakofsky
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D012367:RNA, Viral / Q000096:biosynthesis*; D011995:Recombination, Genetic; D018108:Respirovirus / Q000502:physiology*; D010253:Respirovirus Infections / Q000821:virology*; D017361:Viral Nonstructural Proteins / Q000502:physiology*
chemical_list: D012367:RNA, Viral; D017361:Viral Nonstructural Proteins