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Cell. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus.

Giuseppe

Emeritus
The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. (Cell, abstract, RA-1015, edited)

Cell. 2009 Dec 24;139(7):1243-54.

The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus.

Brass AL, Huang IC, Benita Y, John SP, Krishnan MN, Feeley EM, Ryan BJ, Weyer JL, van der Weyden L, Fikrig E, Adams DJ, Xavier RJ, Farzan M, Elledge SJ. - Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard Medical School, Charlestown, MA 02129, USA. abrass@partners.org

Influenza viruses exploit host cell machinery to replicate, resulting in epidemics of respiratory illness. In turn, the host expresses antiviral restriction factors to defend against infection. To find host cell modifiers of influenza A H1N1 viral infection, we used a functional genomic screen and identified over 120 influenza A virus-dependency factors with roles in endosomal acidification, vesicular trafficking, mitochondrial metabolism, and RNA splicing. We discovered that the interferon-inducible transmembrane proteins IFITM1, 2, and 3 restrict an early step in influenza A viral replication. The IFITM proteins confer basal resistance to influenza A virus but are also inducible by interferons type I and II and are critical for interferon's virustatic actions. Further characterization revealed that the IFITM proteins inhibit the early replication of flaviviruses, including dengue virus and West Nile virus. Collectively this work identifies a family of antiviral restriction factors that mediate cellular innate immunity to at least three major human pathogens.

Copyright 2009 Elsevier Inc. All rights reserved.

PMID: 20064371 [PubMed - in process]

Publication Types:

* Research Support, N.I.H., Extramural
* Research Support, Non-U.S. Gov't

Grant Support:

* AI 50031/AI/NIAID NIH HHS/United States
* AI062773/AI/NIAID NIH HHS/United States
* AI070343/AI/NIAID NIH HHS/United States
* DK043351/DK/NIDDK NIH HHS/United States
* DK060049/DK/NIDDK NIH HHS/United States
* U54 AI057159/AI/NIAID NIH HHS/United States
* Cancer Research UK/United Kingdom
* Howard Hughes Medical Institute/United States
* Wellcome Trust/United Kingdom

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