The induction of interferon by temperature-sensitive mutants of reovirus, UV-irradiated reovirus, and subviral reovirus particles

Abstract

The ability of temperature-sensitive (ts) mutants of reovirus, UV-irradiated reovirus, and subviral particles of reovirus to induce interferon in mouse L929 fibroblasts was investigated. The following results were obtained: 1. 1. Nine ts mutants belonging to six recombination groups induced about the same amount of interferon as wild-type virus at the permissive temperature (31°), but only 1–17% as much at the nonpermissive temperature (38.5°). Mutants capable of synthesizing nearly normal amounts of double-stranded RNA, mRNA, and protein and blocked in a late state of morphogenesis, formed little more interferon than mutants completely blocked in the ability to synthesize double-stranded RNA. The amount of interferon induced did not correlate with any viral function except a very late one which resulted in the formation of intact virions. Although two mutants did induce more interferon (6–13% of wild type) than expected on the basis of their virus yield (about 0.1% of wild type), it was nevertheless concluded that interferon induction elicited by the lytic reovirus multiplication cycle is triggered by some event which depends on the formation of progeny virus particles. 2. 2. The ability to induce interferon is far more resistant to UV irradiation than infectivity: particles which have received 12 inactivating hits can still induce about 25% of normal interferon yields. The effect of UV irradiation on the interferon inducing ability of ts 447 is striking. This is a RNA −mutant which is normally incapable of inducing interferon at 38.5°; on UV-irradiation, it becomes a potent interferon inducer at 38.5°. Cells infected with UV-irradiated wild-type reovirus or ts 447 contain at the most 2% as much virus-specific RNA as cells infected with infectious wild-type virus, and may contain very much less. 3. 3. Reovirus top component particles (which lack RNA) and reovirus cores (which lack the outer capsid shell) induce no interferon, even at multiplicities of 100,000 particles/cell. The nature of the mechanism by which UV-irradiated reovirus induces interferon and of the changes caused in ts 447 by UV irradiation which convert it to a potent interferon inducer at 38.5° are discussed in the light of the lack of interferon inducing ability of empty virus particles and cores, and of the absence of virus-specific RNA in infected cells. The mechanism by which UV-irradiated reovirus induces interferon appears to differ from that by which interferon is induced during the productive lytic reovirus infection cycle.