STUDIES ON AN INTERFERON SENSITIVE MUTANT OF MENGOVIRUS

There are many genes for both leukocyte and fibroblast interferon; and each may induce a different array of antiviral or anticellular activities. Although much is known about some of these activities from in vitro studies, their role in vivo is unclear. In this thesis the physical and biological properties of a unique interferon response mutant of mengovirus (is-1) were studied. I have used this mutant to identify 2 distinct antiviral activities operating in interferon protected L cells. The first antiviral activity (AVA-1) primarily delays virus RNA and protein syntheses and thereby lengthens the virus replication cycle. At the interferon levels used, it does not greatly reduce the final yield of the parent virus, is(\u27+), and all cells die from the infection. A protein kinase which inactivates an initiation factor for protein synthesis (eIF-2) may play a key role in this activity. The second antiviral activity (AVA-2) appears to be a previously uncharacterized nuclease with a half life of about 1.5 hours. It does not prevent the virus induced inhibition of host macromolecular syntheses, but inhibits all other virus functions. At 9 to 12 hours after infection host syntheses resumes and most cells survive the infection. The data suggest that some step in the virus replication cycle activates this activity leading to the destruction of the is-1 genome between 6 and 12 hours after infection. Actinomycin D or 1,6-dichloro-1-(beta)-D-ribofuranosylbenzimidazole (DRB) added at the time of infection reverses the is-1 phenotype. Under these conditions is-1 responds to antiviral activity 1 and the time course of is(\u27+) and is-1 growth are identical. In unprotected cells the yields of the 2 viruses were similar. No quantitative or qualitative differences in virus products were observed, even when proteins were examined by 2 dimensional gel electrophoresis. However, co-infection of is-1 infected cells with is(\u27+) or vaccinia virus phenotypically reverted is-1 to is(\u27+). It is unlikely that the synthesis of antiviral activity 2 is specifically inhibited by is(\u27+), because both viruses appear to have the same effect on host macromolecular syntheses. Therefore, the is-1 virus seems to have lost a wild type function which normally blocks the action of antiviral activity 2