@article{5aeabc6b0030485e95de4d0cbbd48e04,
title = "Amphotericin B Increases Influenza A Virus Infection by Preventing IFITM3-Mediated Restriction",
abstract = "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.",
author = "Lin, {Tsai Yu} and Chin, {Christopher R.} and Everitt, {Aaron R.} and Simon Clare and Perreira, {Jill M.} and George Savidis and Aker, {Aaron M.} and John, {Sinu P.} and David Sarlah and Carreira, {Erick M.} and Elledge, {Stephen J.} and Paul Kellam and Brass, {Abraham L.}",
note = "Funding Information: We thank University of Massachusetts Medical School (UMMS) colleagues R. Fish, B. Hobbs, L. Benson, T. Brailey, and J. Barrett and Ragon Institute colleagues M. Boyarina, K. Donnelly, and P. Richtmeyer. We thank A.T. Chan (Massachusetts General Hospital), A. Quaresma and J. Nickerson (UMMS), J. White (University of Virginia), K. Weninger (North Carolina State University), and G. Melikian (Emory University) for helpful discussions and advice. This work was generously supported by a grant (1R01AI091786) from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (to A.L.B.). A.L.B. is grateful to the Charles H. Hood Foundation, the Burroughs Wellcome Fund, the Bill and Melinda Gates Foundation, the Phillip T. and Susan M. Ragon Foundation, and the Harvard and UMMS Centers for AIDS Research for their generous support. P.K, S.C., and A.R.E are supported by the Wellcome Trust. S.J.E. is a Howard Hughes Investigator. ",
year = "2013",
month = nov,
day = "27",
doi = "10.1016/j.celrep.2013.10.033",
language = "English (US)",
volume = "5",
pages = "895--908",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "4",
}