The IFITM Proteins Mediate Cellular Resistance to Influenza A H1N1 Virus, West Nile Virus, and Dengue Virus

Brass, A.L., et al. Cell 139, 1243-1254 (2009)

Speacker : Kuan-Ru Chen (陳冠儒)             Time: 15:00~16:00

Commentator: Dr. Shun-Hua Chen (陳舜華)               Place: Room 601

Abstract:

Influenza A virus belongs to the orthomyxoviruses family and causes epidemics or pandemics of respiratory diseases in human. Because its high mutation rates facilitate the generation of viral escape strains, the available vaccines and drugs are not always effective. Previous studies indicated that identification of the host factors participating in virus replication can provide valuable new targets for antiviral therapy. Additionally, RNA interference (RNAi) screen is useful to dissect virus-host cell interaction. In this paper, the authors performed RNAi screen to identify host factors that modify influenza virus infection. By this screen, the authors identified over 120 host factors required for influenza A virus replication. They discovered that silencing of interferon-inducible transmembrane proteins (IFITM) 3 led to the increase of influenza A virus replication and IFITM3 was also required for the antiviral actions of interferon. IFITM 3 and its paralogs could inhibit the early replication of influenza A virus, and they also used ifitm knockout cell to confirm that ifitm is an influenza A virus restriction factor. Furthermore, they also found that the IFITM proteins could inhibit the early replication of flaviviruses, including West Nile virus and dengue virus. Thus, this study provided an integrated model of influenza A virus-host cell interaction by RNAi screen, and revealed potential antiviral targets. They discovered that IFITM proteins as antiviral agents for influenza virus, West Nile virus and Dengue virus.

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