Correlation between interferon sensitivity of reovirus isolates and ability to discriminate between normal and Ras-transformed cells.
Mammalian reoviruses exhibit a propensity to replicate in transformed cells. It is currently believed that the interferon-inducible RNA-dependent protein kinase (PKR), an intracellular host-cell resistance factor that is inhibited by an activated Ras-dependent pathway in transformed cells, is responsible for this discrimination. In the present study, reovirus isolates differing in their sensitivity to interferon were obtained by chemical mutagenesis, and examined for their replicative properties in parental and Ras-transformed mouse NIH-3T3 cells. It was observed that most isolates can bypass resistance mechanisms of parental cells at high m.o.i., and that there is a correlation between the ability to discriminate between transformed and parental cells, and interferon sensitivity. Most interestingly, an interferon-hypersensitive mutant virus was more dependent on Ras activation than any other viral isolate. Altogether, this suggests that optimal reovirus isolates could be selected to attack tumour cells depending on the nature of the alterations in interferon-inducible pathways found in these cells.
Rudd
Penny
P
Département de Microbiologie et Immunologie, Université de Montréal, PO Box 6128, Station centre-ville, Montréal, Québec, Canada, H3C 3J7.
Lemay
Guy
G
Département de Microbiologie et Immunologie, Université de Montréal, PO Box 6128, Station centre-ville, Montréal, Québec, Canada, H3C 3J7.
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D007372:Interferons / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D016296:Mutagenesis; D030102:Orthoreovirus, Mammalian / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*
D000998:Antiviral Agents; D007372:Interferons