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Amphotericin B Increases Influenza A Virus Infection by Preventing IFITM3-Mediated Restriction

2013; Cell Press; Volume: 5; Issue: 4 Linguagem: Inglês

10.1016/j.celrep.2013.10.033

2639-1856

Tsai‐Yu Lin, Christopher R. Chin, Aaron R. Everitt, Simon Clare, Jill M. Perreira, George Savidis, Aaron M. Aker, Sinu P. John, David Šarlah, Erick M. Carreira, Stephen J. Elledge, Paul Kellam, Abraham L. Brass,

Antimicrobial Peptides and Activities

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.