nystatin-a1 and Influenza--Human

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.

Topics: Acetylcholine; Amphotericin B; Animals; Anti-Bacterial Agents; Antifungal Agents; Antigens, Differentiation; Biological Transport; Cell Fusion; Cell Line; Cell Membrane; Chlorocebus aethiops; COS Cells; 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

Topics: Candidiasis; Geriatrics; Humans; Influenza, Human; Lung Diseases, Fungal; Mycoses; Nystatin; Pneumonia

Topics: Aerosols; Animals; Candidiasis; Humans; Influenza, Human; Nystatin; Pneumonia; Rats; Sodium