Inhibitory effect of bafilomycin A1, a specific inhibitor of vacuolar-type proton pump, on the growth of influenza A and B viruses in MDCK cells.
We studied the effect of bafilomycin A1 (Baf-A1), a novel and highly specific 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 complete disappearance of acidified compartments such as endosomes and lysosomes both in infected and uninfected cells by the treatment with 0.1 microM inhibitor for 1 h at 37 degrees C. In addition, virus growth was inhibited when Baf-A1 was present from 1 h before infection to the end of incubation, or added within as early as 5-10 min after infection. Conversely, the virus growth was recovered in correlation with the reappearance of acidified compartments after removal of Baf-A1. These data suggest that Baf-A1-sensitive V-H+ pumps are solely responsible for the acidification of endosomes and lysosomes, and thus Baf-A1 inhibits the growth of influenza A and B viruses by affecting the acidified compartments in which low pH is essential for the uncoating process of influenza virus growth at an early stage of infection.
Ochiai
H
H
Department of Human Science and Fundamental Nursing, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Sakai
S
S
Hirabayashi
T
T
Shimizu
Y
Y
Terasawa
K
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004285:Dogs; D011992:Endosomes / Q000187:drug effects; D009980:Influenza A virus / Q000187:drug effects* / Q000254:growth & development; D009981:Influenza B virus / Q000187:drug effects* / Q000254:growth & development; D007668:Kidney / Q000166:cytology; D008247:Lysosomes / Q000187:drug effects; D018942:Macrolides; D054328:Proton Pump Inhibitors
D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D018942:Macrolides; D054328:Proton Pump Inhibitors; C040929:bafilomycin A1