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

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

Research output: Contribution to journalArticlepeer-review


The IFITMs inhibit influenza A virus (IAV) replication invitro and invivo. Here, we establish that the antimycotic heptaen, amphotericin B (AmphoB), preventsIFITM3-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 invitro. Mechanistic studies reveal that IFITM1 decreases host-membrane fluidity, suggesting both a possible mechanism for IFITM-mediated restriction and itsnegation by AmphoB. Notably, we reveal that micetreated with AmBisome succumbed to a normally mild IAV infection, similar to animals deficient inIfitm3. 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.

Original languageEnglish (US)
Pages (from-to)895-908
Number of pages14
JournalCell Reports
Issue number4
StatePublished - Nov 27 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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