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.
Department of Human Science and Fundamental Nursing, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
H
H
Ochiai
S
S
Sakai
T
T
Hirabayashi
Y
Y
Shimizu
K
K
Terasawa
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