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


Date

2013-11

Publication Type

Journal Article

ETH Bibliography

yes

Citations

Altmetric

Data

Abstract

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.

Publication status

published

Editor

Book title

Journal / series

Volume

5 (4)

Pages / Article No.

895 - 908

Publisher

Elsevier

Event

Edition / version

Methods

Software

Geographic location

Date collected

Date created

Subject

Organisational unit

03511 - Carreira, Erick M. / Carreira, Erick M. check_circle

Notes

Funding

Related publications and datasets