Induction of an antiviral state by interferon in the absence of elevated levels of 2,5-oligo(A) synthetase and eIF-2 kinase

Abstract

A series of clones has been derived from an interferon-resistant murine cell line, Ltk − aprt −, and their antiviral properties have been characterized. In the parental Ltk − aprt − line interferon is unable to establish antiviral properties or to increase the levels of 2,5-oligo(A) synthetase, the 2,5-oligo(A)-activated endonuclease F, 2′,5′-phosphodiesterase, or eIF-2 kinase. However, interferon did prevent replication of vesicular stomatitis, Mango virus, and reovirus in some of the derivative cell lines. The effect of interferon on the levels of the enzymes of the 2,5-oligo(A) and eIF-2 kinase pathways did not correlate directly with the antiviral properties of these cell clones. Greatly increased levels of 2,5-oligo(A) synthetase occurred in one clone without activation of an antiviral state. Another clone exhibited antiviral activity without detectably increased 2,5-oligo(A) synthetase activity. Changes in the levels of endonuclease F and 2′,5′-phosphodiesterase were slight in all the clones examined. Neither 2,5-oligo(A) synthetase nor eIF-2 kinase levels were altered by interferon in another clone and yet an antiviral state was established and prevented replication of vesicular stomatitis, Mango virus, and reovirus. The results show that mechanisms other than the 2,5-oligo(A) and elF-2 kinase pathways are likely to contribute to the antiviral effects of interferon.