title: Semliki forest virus neurovirulence mutants have altered cytopathogenicity for central nervous system cells.
abstract: We have analyzed the pathogenicity and host range properties of four neurovirulence mutants of Semliki Forest virus which, unlike the wild type (WT), allow the survival of weanling mice injected intraperitoneally with 10(2) PFU. The mutant M9 showed a sustained multiplication in the brains of infected mice. It produced paralysis in 35%, and 8% died. Demyelination occurred in 94% of the surviving mice and was associated with the destruction of oligodendrocytes. All of the mutants showed a restricted ability to multiply in BHK, C1300 (neuroblastoma), and G26-24 (oligodendroglioma) cells as compared with the WT, and this was not associated with differential interferon production or action. C1300 cells infected with the mutants survived, whereas WT-infected cells were killed. In G26-24 cells all of the mutants and the WT produced a rapid cytopathic effect which was inhibited by pretreatment with 10 U of mouse interferon. Extensive RNA synthesis was detected for all of the mutants and the WT in BHK and C1300 cells, but it was only detectable in G26-24 cells in small amounts early in the infection. The mutant M4 had a defect in the nucleocapsid assembly, whereas M9 had a defect in total RNA synthesis. M136 was defective in the synthesis of 26S RNA, and M103 showed defective synthesis of viral core protein in C1300 cells. It is concluded that C1300 cells can tolerate viral RNA synthesis by a defective virus without showing a cytopathic effect, but the fully virulent WT virus is cytopathic. G26-24 cells are sensitive to small amounts of viral RNA synthesis. These properties of the WT and mutant viruses correlate with changes produced in the neurons and oligodendrocytes of the central nervous system: the virulence of the WT is due to its ability to destroy both neurons and oligodendrocytes, whereas the demyelination produced by the mutants M9 and M136 is due to the destruction of oligodendrocytes alone.
mesh_terms: D000818:Animals; D002213:Capsid / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D003588:Cytopathogenic Effect, Viral; D007372:Interferons / Q000096:biosynthesis / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009447:Neuroblastoma; D009457:Neuroglia / Q000382:microbiology*; D009474:Neurons / Q000382:microbiology*; D009836:Oligodendroglia / Q000382:microbiology*; D012367:RNA, Viral / Q000096:biosynthesis; D012672:Semliki forest virus / Q000472:pathogenicity* / Q000502:physiology; D014764:Viral Proteins / Q000096:biosynthesis
chemical_list: D012367:RNA, Viral; D014764:Viral Proteins; D007372:Interferons