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Cell Reports, 21 November 2013
Copyright ? 2013 The Authors
10.1016/j.celrep.2013.10.033
This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
Authors
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. Brasssend emailSee Affiliations
Highlights
Amphotericin B or AmBisome prevents IFITM3-mediated restriction of IAV
AmBisome overcomes the majority of IFN?s antiviral effects in vitro
IFITM1 decreases membrane fluidity and inhibits membrane fusion
AmBisome increases the morbidity and mortality of influenza
Summary
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.
