Inhibitors of prostaglandin synthesis inhibit growth of human cytomegalovirus and reactivation of latent virus in a productively and latently infected human cell line.

Indomethacin and tetracaine, inhibitors of prostaglandin synthesis, inhibited production of infectious human cytomegalovirus (HCMV) in a human thyroid papillary carcinoma cell line (TPC-1) by 99.9% when added to cultures at the concentration of 2 x 10(-4) M during the first 24 hr after infection. Although immediate early virus proteins were synthesized at similar molar ratios in mock- and compound-treated cultures, induction of HCMV-specific DNA polymerase (one of the early virus proteins) was inhibited by treatment with these compounds, suggesting that the early stages of the virus growth cycle are most likely to be under the control of indomethacin or tetracaine action. We have previously developed an in vitro HCMV latency model system in TPC-1 cultures. This system was used to study the effect of these compounds on reactivation of the latent virus. When TPC-1 cultures preheated for 48 hr at 40.5 degrees were infected with HCMV and incubated at 40.5 degrees, the cultures could be maintained for 30 days without detection of infectious virus. The latent HCMV was reactivated within 10 days by reducing the incubation temperature from 40.5 to 37 degrees. However, when the latently infected cultures were treated with indomethacin or tetracaine immediately after being shifted to 37 degrees, reactivation of the latent virus was not observed.