Influence of trifluoperazine on the late stage of influenza virus infection in MDCK cells.

We investigated the influence of the anticalmodulin drug, trifluoperazine (TFP) on influenza virus growth in MDCK cells. The inhibitory effect of TFP on virus growth was observed even when TFP was added at a late stage of infection. This inhibitory effect was concentration-dependent in the concentration range of 20-35 microM. At 35 microM, TFP caused a complete alteration in the distribution pattern of hemagglutinin (HA), concomitant with a decrease in the appearance of HA on the cell surface. After removal of the drug, the HA gradually began to show a normal distribution pattern and reappeared on the cell surface. The time course of rearrangement of HA was in accord with that of the recovery of cell supernatant infectivity. Scanning electron microscopic study revealed that the drug did not cause accumulation of the progeny viruses on the cell surface. The drug effect on the virus growth was reversed by the simultaneous presence of purified calmodulin (CaM). These data suggest that TFP acts as a reversible inhibitor of influenza virus morphogenesis, but not budding, by disturbing cellular CaM and/or CaM-dependent functions.