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Bafilomycin A<jats:sub>1<\/jats:sub>(Baf-A<jats:sub>1<\/jats:sub>), when used at relative high concentrations (\u226510 nM), inhibits vacuolar ATPase (V-ATPase) and reduces endosome acidification and lysosome number, thus inhibiting IAV replication but promoting host cell cytotoxicity. We tested the hypothesis that much lower doses of Baf-A<jats:sub>1<\/jats:sub>also have anti-IAV activity, but without toxic effects. Thus we assessed the antiviral activity of Baf-A<jats:sub>1<\/jats:sub>at different concentrations (0.1\u2013100 nM) in human alveolar epithelial cells (A549) infected with IAV strain A\/PR\/8\/34 virus (H1N1). Infected and mock-infected cells pre- and cotreated with Baf-A<jats:sub>1<\/jats:sub>were harvested 0\u201324 h postinfection and analyzed by immunoblotting, immunofluorescence, and confocal and electron microscopy. We found that Baf-A<jats:sub>1<\/jats:sub>had disparate concentration-dependent effects on subcellular organelles and suppressed affected IAV replication. At concentrations \u226510 nM Baf-A<jats:sub>1<\/jats:sub>inhibited acid lysosome formation, which resulted in greatly reduced IAV replication and release. Notably, at a very low concentration of 0.1 nM that is insufficient to reduce lysosome number, Baf-A<jats:sub>1<\/jats:sub>retained the capacity to significantly impair IAV nuclear accumulation as well as IAV replication and release. In contrast to the effects of high concentrations of Baf-A<jats:sub>1<\/jats:sub>, very low concentrations did not exhibit cytotoxic effects or induce apoptotic cell death, based on morphological and FACS analyses. In conclusion, our results reveal that low-concentration Baf-A<jats:sub>1<\/jats:sub>is an effective inhibitor of IAV replication, without impacting host cell viability.<\/jats:p>","DOI":"10.1152\/ajplung.00011.2014","type":"journal-article","created":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T09:10:30Z","timestamp":1414833030000},"page":"L270-L286","source":"Crossref","is-referenced-by-count":81,"title":["Suppression of influenza A virus replication in human lung epithelial cells by noncytotoxic concentrations bafilomycin A1"],"prefix":"10.1152","volume":"308","author":[{"given":"Behzad","family":"Yeganeh","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada;"},{"name":"Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeid","family":"Ghavami","sequence":"additional","affiliation":[{"name":"Department of 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