Amphotericin B Increases Influenza A Virus Infection by Preventing IFITM3-Mediated Restriction
The IFITMs inhibit influenza A virus (IAV) replication in vitro and in vivo. Here, we establish that the antimycotic heptaen, amphotericin B (AmphoB), prevents IFITM3-mediated restriction of IAV, thereby increasing viral replication. Consistent with its neutralization of IFITM3, a clinical preparat...
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doaj-f5e7ef117daf469eac6a2181bd278b4f2020-11-24T21:33:41ZengElsevierCell Reports2211-12472013-11-015489590810.1016/j.celrep.2013.10.033Amphotericin B Increases Influenza A Virus Infection by Preventing IFITM3-Mediated RestrictionTsai-Yu Lin0Christopher R. Chin1Aaron R. Everitt2Simon Clare3Jill M. Perreira4George Savidis5Aaron M. Aker6Sinu P. John7David Sarlah8Erick M. Carreira9Stephen J. Elledge10Paul Kellam11Abraham L. Brass12Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, USADepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, USAWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UKWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UKDepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, USADepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, USADepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, USARagon Institute of Massachusetts General Hospital, M.I.T. and Harvard University, Charlestown, MA 02129, USAEidgenössische Technische Hochschule, Deutsch English Department of Chemistry and Applied Biosciences, 8093 Zurich, SwitzerlandEidgenössische Technische Hochschule, Deutsch English Department of Chemistry and Applied Biosciences, 8093 Zurich, SwitzerlandDepartment of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USAWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UKDepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, USA The IFITMs inhibit influenza A virus (IAV) replication in vitro and in vivo. Here, we establish that the antimycotic heptaen, amphotericin B (AmphoB), prevents IFITM3-mediated restriction of IAV, thereby increasing viral replication. Consistent with its neutralization of IFITM3, a clinical preparation of AmphoB, AmBisome, reduces the majority of interferon’s protective effect against IAV in vitro. Mechanistic studies reveal that IFITM1 decreases host-membrane fluidity, suggesting both a possible mechanism for IFITM-mediated restriction and its negation by AmphoB. Notably, we reveal that mice treated with AmBisome succumbed to a normally mild IAV infection, similar to animals deficient in Ifitm3. Therefore, patients receiving antifungal therapy with clinical preparations of AmphoB may be functionally immunocompromised and thus more vulnerable to influenza, as well as other IFITM3-restricted viral infections. http://www.sciencedirect.com/science/article/pii/S2211124713006177 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tsai-Yu Lin Christopher R. Chin Aaron R. Everitt Simon Clare Jill M. Perreira George Savidis Aaron M. Aker Sinu P. John David Sarlah Erick M. Carreira Stephen J. Elledge Paul Kellam Abraham L. Brass |
spellingShingle |
Tsai-Yu Lin Christopher R. Chin Aaron R. Everitt Simon Clare Jill M. Perreira George Savidis Aaron M. Aker Sinu P. John David Sarlah Erick M. Carreira Stephen J. Elledge Paul Kellam Abraham L. Brass Amphotericin B Increases Influenza A Virus Infection by Preventing IFITM3-Mediated Restriction Cell Reports |
author_facet |
Tsai-Yu Lin Christopher R. Chin Aaron R. Everitt Simon Clare Jill M. Perreira George Savidis Aaron M. Aker Sinu P. John David Sarlah Erick M. Carreira Stephen J. Elledge Paul Kellam Abraham L. Brass |
author_sort |
Tsai-Yu Lin |
title |
Amphotericin B Increases Influenza A Virus Infection by Preventing IFITM3-Mediated Restriction |
title_short |
Amphotericin B Increases Influenza A Virus Infection by Preventing IFITM3-Mediated Restriction |
title_full |
Amphotericin B Increases Influenza A Virus Infection by Preventing IFITM3-Mediated Restriction |
title_fullStr |
Amphotericin B Increases Influenza A Virus Infection by Preventing IFITM3-Mediated Restriction |
title_full_unstemmed |
Amphotericin B Increases Influenza A Virus Infection by Preventing IFITM3-Mediated Restriction |
title_sort |
amphotericin b increases influenza a virus infection by preventing ifitm3-mediated restriction |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2013-11-01 |
description |
The IFITMs inhibit influenza A virus (IAV) replication in vitro and in vivo. Here, we establish that the antimycotic heptaen, amphotericin B (AmphoB), prevents IFITM3-mediated restriction of IAV, thereby increasing viral replication. Consistent with its neutralization of IFITM3, a clinical preparation of AmphoB, AmBisome, reduces the majority of interferon’s protective effect against IAV in vitro. Mechanistic studies reveal that IFITM1 decreases host-membrane fluidity, suggesting both a possible mechanism for IFITM-mediated restriction and its negation by AmphoB. Notably, we reveal that mice treated with AmBisome succumbed to a normally mild IAV infection, similar to animals deficient in Ifitm3. Therefore, patients receiving antifungal therapy with clinical preparations of AmphoB may be functionally immunocompromised and thus more vulnerable to influenza, as well as other IFITM3-restricted viral infections.
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url |
http://www.sciencedirect.com/science/article/pii/S2211124713006177 |
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