Host Modulagtors of the Death Response to Influenza a Infection

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Title: Host Modulagtors of the Death Response to Influenza a Infection
Author: Ward, Samuel Enoch
Abstract: Influenza A virus infects 5 -20 % of the population annually , resulting in ~35 ,000 deaths and significant morbidity . Current treatments include vaccines and drugs that target viral proteins . However , both of these approaches have limitations , as vaccines require yearly development and the rapid evolution of viral proteins gives rise to drug resistance . In consequence additional intervention strategies , that target host factors required for the viral life cycle , are under investigation . Here I employed arrayed whole -genome siRNA screening strategies to identify cell -autonomous molecular components that are subverted to support H1N1 influenza A virus infection of human mucosal epithelial cells . Integration across relevant public data sets exposed druggable gene products required for epithelial cell infection or required for viral proteins to deflect host cell suicide checkpoint activation . Pharmacological inhibition of representative targets , RGGT and CHEK1 , resulted in significant protection against infection of human epithelial cells by the A /WS /33 virus . In addition , chemical inhibition of RGGT partially protected against H5N1 and the 2009 H1N1 pandemic strain . The observations reported here thus contribute to decoding vulnerabilities in the command and control networks specified by influenza virulence factors . [Keywords : Influenza A , genomewide screen , RNAi , innate immunity , CHEK1 , IFITM3 , virus]
URI: http : / /hdl .handle .net /2152 .5 /1008
Date: 2012-07-17


Host Modulagtors of the Death Response to Influenza a Infection. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /1008 .

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