Participation of DNA-dependent RNA polymerase II in replication of influenza viruses

Abstract

FOR many years it has been known that inhibitors of the expression of cell DNA, such as actinomycin D, prevent the multiplication of influenza viruses; inhibitors of DNA synthesis have no such effect^1–3. This phenomenon is still not understood, even though from the outset the available data have suggested that cell gene transcription may be a necessary prerequisite for virus RNA transcription and replication². The discovery that α-amanitin, a specific inhibitor of nucleoplasmic DNA-dependent RNA polymerase II (ref. 4), also specifically inhibits influenza virus replication^5,6, is additional support for the theory that cell gene expression is essential for virus growth. There has always been the possibility, however, that inhibition of virus growth is unrelated to the defined activities of DNA function inhibitors. It is possible, for example, that actinomycin D or α-amanitin might prevent the uptake or uncoating of influenza viruses, might inhibit directly the virion-associated transcriptase in vivo, or might act in some other unrecognised way. We describe here experiments in which α-amanitin was tested for its ability to inhibit the growth of influenza virus in cells containing an α-amanitin-resistant DNA-dependent RNA polymerase; in these circumstances, the virus grows normally in the presence of high concentrations of α-amanitin. This finding indicates that DNA-dependent RNA polymerase II has an essential role in the replication of influenza viruses.