Inhibition of semliki forest and herpes simplex virus production i α‐difluoromethylornithine‐treated cells: Reversal by polyamines

The suggested importance of the natural polyamines putrescine, spermidine and spermine in the macromolecular synthesis and proliferation of animal cells .[ 1,2] has generally been confirmed by results obtained with inhibitors of polyamine synthesis. However, studies of virus production in the inhibitortreated cells which could serve as a model system to explore the cellular function(s) of polyamlnes, have revealed conflicting results. A decrease of the formation of vaccinia virus and human cytomegalovirus (HCMV) has been observed [3-51 in cells treated with methylglyoxal bis(guanylhydrazone), an inhibitor of S-adenosylrnethionine decarboxylase (EC 4.1 .l SO), whereas this drug did not affect [4,6] the production of herpes simplex viruses (HSV-1 and HSV-2). Similarly, D ,L-cll-methylornithine , a competitive inhibitor of omithlne decarboxylase (EC 4.1 .1.17), had no effect on the replication of HSV-1 and HSV-2, but decreased the production of HCMV [4]. However, in [7] no effect on the HCMV synthesis was observed in cells treated with o-methylomithine or its derivative, D,Ladifluoromethylomithine (DFMO). Further studies of this system seemed therefore desirable, with special attention being paid to the effect of the experimental set-up and the specificity of the action of the inhibitor. Here, we show that the production of two different types of viruses, HSV-2 and Semliki Forest virus, is inhibited in cells pretreated with DMFO. This inhibition could be abolished by exogenous polyamines.