Inhibition of Pichinde virus replication by actinomycin D

The yields of Pichinde virus, a member of the arenavirus group, were markedly inhibited when infected BHK 21 cells were incubated in the presence of 0.4 to 4 mug/ml of actinomycin D. Maximal inhibition was observed when actinomycin D was added after the adsorption of virus to cultures; however, addition of drug as late as 12 h after infection reduced the 24 h yield by 50%. Virus antigen synthesis, as measured by complement fixation and immunodiffusion, was not dramatically reduced by actinomycin D. The expression of virus antigens on the surface of infected cells was greater on cells treated with actinomycin D than on untreated cells. Putative defective particles with a density of Pichinde virus were not detected in fluids of cultures incubated with actinomycin D and 3H-amino acids. Actinomycin D appears to inhibit Pichinde virus late in the replicative cycle. The observations raise the possibility that the drug inhibits the synthesis of proteins of the host cell membrane which are required for virus maturation.