Department of Microbiology and Physiological Systems
Acetylcholine; Amphotericin B; Animals; Anti-Bacterial Agents; Antifungal Agents; Antigens, Differentiation; Biological Transport; COS Cells; Cell Fusion; Cell Line; Cell Membrane; Cercopithecus aethiops; HeLa Cells; Humans; *Immunocompromised Host; Influenza A Virus, H1N1 Subtype; Influenza, Human; Interferons; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Nystatin; Orthomyxoviridae Infections; RNA Interference; RNA, Small Interfering; Sodium; Tetraethylammonium; Virus Internalization; Virus Replication
Immunology of Infectious Disease | Immunopathology | Immunoprophylaxis and Therapy | Influenza Humans | Virology
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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Citation: Cell Rep. 2013 Nov 27;5(4):895-908. doi: 10.1016/j.celrep.2013.10.033. Epub 2013 Nov 21. Link to article on publisher's site
Lin, Tsai-Yu; Chin, Christopher R.; Everitt, Aaron R.; Clare, Simon; Perreira, Jill; Savidis, George; Aker, Aaron M.; John, Sinu P.; Sarlah, David; Carreira, Erick M.; Elledge, Stephen J.; Kellam, Paul; and Brass, Abraham L., "Amphotericin B increases influenza A virus infection by preventing IFITM3-mediated restriction" (2013). University of Massachusetts Medical School Faculty Publications. 805.
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