INHIBITORY EFFECT OF BAFILOMYCIN A1, A SPECIFIC INHIBITOR OF VACUOLAR-TYPE PROTON PUMP, ON THE GROWTH OF INFLUENZA-A AND INFLUENZA-B VIRUSES IN MDCK CELLS

We studied the effect of bafilomycin Al (Baf-A1), a novel and highly s pecific inhibitor for vacuolar-type proton (V-H+) pump, on the growth of influenza A and B viruses in Madin-Darby canine kidney cells. Vital fluorescence microscopic study showed that Baf-A1 induced the complet e disappearance of acidified compartments such as endosomes and lysoso mes both in infected and uninfected cells by the treatment with 0.1 mu M inhibitor for 1 h at 37 degrees C. In addition, virus growth was in hibited when Baf-A1 was present from 1 h before infection to the end o f incubation, or added within as early as 5-10 min after infection. Co nversely, the virus growth was recovered in correlation with the reapp earance of acidified compartments after removal of Baf-A1. These data suggest that Baf-A1-sensitive V-H+ pumps are solely responsible for th e acidification of endosomes and lysosomes, and thus Baf-A1 inhibits t he growth of influenza A and B viruses by affecting the acidified comp artments in which low pH is essential for the uncoating process of inf luenza virus growth at an early stage of infection.