Reversible inhibition of cytomegalovirus replication by phosphonoformate

Abstract

Cytomegalovirus (CMV Ad. 169)-induced late antigens are specifically inhibited by phosphonoformate (PFA). Four fresh isolates of CMV were also inhibited by PFA to varying degrees. The kinetics of CMV immediate early antigens (IEA) and early nuclear antigens (EA) produced in the presence of PFA were compared to the early phase of the replicative infection. After anticomplement immunofluorescence with anti-IEA and anti-EA, microimmunofluorometry of individual CMV-infected nuclei was performed. CMV-induced antigens had a two-wave appearance, with maxima at 6 and 24 h postinfection. The same was seen in the presence of PFA. CMV EA-containing cells persisted for more than 5 weeks in the presence of PFA, but decreased in frequency and antigen content. The inhibition of virus replication was reversible after all incubation periods assayed. After PFA release, IEA and EA appeared again in many cells, and the kinetics were similar to that of initial infection. The results suggest that the input CMV genome persists in most initially infected cells, survives PFA incubation, and is active again after PFA release. This differs from abortive CMV infections.