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Association between influenza virus RNA polymerase and the transcriptional machinery of the host cell (FLU-POLII)
Date du début: 1 avr. 2014, Date de fin: 31 mars 2016 PROJET  TERMINÉ 

Influenza infections represent a worldwide problem both in terms of public health and economic consequences. Seasonal influenza epidemics affect 3 to 5 million people annually and are estimated to cause 250,000-500,000 deaths globally. Besides, recurrent pandemics are a serious threat because novel viruses can emerge to which the population has no pre-existing immunity. In the event of such a situation, existing vaccines would be unlikely to be effective and production of a vaccine matching the pandemic virus would require several months. In addition, existing antiviral treatments are very limited and development of resistance by the virus would reduce their effectiveness. Thus, there is clearly an urgent need to develop new treatments for the control of influenza.The viral RNA polymerase is at the core of the transcription and replication complex of influenza virus and it is a crucial factor for pathogenicity and host restriction. Its activity is regulated by interactions with the host cell. Previous research in the host group has shown that the viral polymerase interacts with cellular RNA polymerase II (Pol II), but many aspects of this interaction remain unclear and its biological role is not known. This project will explore this interaction under the hypothesis that it is required for synthesis of viral mRNA. We will map the Pol II-binding domain of the viral polymerase. If the interaction is not direct we will identify the mediating factor(s) using proteomic approaches. The functional significance of the association between viral polymerase and Poll II will be investigated in vivo using a combination of reverse genetics and ChIP-sequencing approaches. This project is expected to identify novel druggable targets where essential interactions between the viral machinery and host cell factors can be disrupted, which may ultimately lead to the development of new antiviral drugs against influenza infection.