Cellular DNA synthesis associated with activation of latent herpes simplex virus in cell culture

Herpes simplex virus type 1 (HSV-1) latency was established in human embryo lung (HEL) cells by treatment with (E)-5-(2'-bromovinyl)-2'-deoxyuridine and human leukocyte interferon and subsequent temperature increase (from 37 degrees to 40.5 degrees). This in vitro system was used to study reactivation after temperature shift-down to 37 degrees. Four methods known to induce cell DNA synthesis, superinfection with human cytomegalovirus, increased serum concentration in the medium, wound production, and superinfection with simian virus 40 (SV40), accelerated activation and replication of HSV-1. In contrast, reduced serum concentration resulted in postponement of virus reactivation and lower yield. In control experiments with mock-infected HEL cells treated with inhibitors and maintained for prolonged periods of time at 40.5 degrees, [3H]-thymidine incorporation was stimulated by increased serum concentration in the medium, wounding and SV40 superinfection, and hampered by reduced serum concentration in the medium. The data seem to indicate that cell DNA synthesis, the processes associated with it, or both, play a key role in the activation of latent HSV-1 and subsequent virus replication in this system.