Dissociable antiviral activities directed against cardioviruses are expressed in L cells treated with interferon

Interferon (IFN) restricts a wide variety of viruses. To do so it elicits many antiviral pathways. For example, subclones of the same cell line with a reduced antiviral spectrum are thought to lack one or more antiviral pathways. Our line of L cells exhibits two distinct antiviral activities. The first delays the yield of both wild-type mengovirus (is+) and an IFN-sensitive mutant (is-1). The second specifically inhibits is-1 virus yields 100-fold. From these cells, a subclone was isolated which had lost the second antiviral activity (i.e. in these cells is-1 virus acts like is+ virus). To see whether other cardioviruses are sensitive to these activities, two additional strains [m-mengovirus and encephalomyocarditis-R (EMC-R) virus] were tested in our subclones. Like is+ virus, m-mengovirus yields were delayed by IFN in both subclones; EMC-R virus behaved like is-1 virus in both cell lines. When actinomycin D was added at the time of infection, is-1 virus was phenotypically reversed to is+ virus, but EMC-R virus was still inhibited. The 2-5A synthetase/RNase L pathway is expressed in both clones. Therefore, at least three antiviral activities against cardioviruses can be distinguished in IFN-treated L cells, and two of them appear not to involve the 2-5A synthetase/RNase L pathway.