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Recrutement des kinases PI4KIII aux organelles de réplication virale au cours de l’infection par le poliovirus et d’autres virus à ARN de polarité positive Volume 18, issue 5, Septembre-Octobre 2014

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Authors
1 Institut Pasteur, Unité de biologie des virus entériques, 28, rue du Docteur-Roux, 75724 Paris cedex 15, France
2 Inserm U994, Institut Pasteur, 75724 Paris, France
3 Université Versailles Saint-Quentin, 78000 Versailles, France
4 Université Paris-Diderot, Sorbonne Paris-Cité, Cellule Pasteur, 75013 Paris, France
* Tirés à part

One characteristic of infections with RNA viruses of positive polarity is the generation of new specialized membrane structures acting as platforms accommodating the complexes involved in replication of the viral genome. The functionality of these “replication organelles” is dependent on interactions between viral nonstructural proteins, recruited host factors and viral RNAs. Poliovirus, the causal agent of paralytic poliomyelitis, is the model most frequently used for identification of the viral and cellular components involved in this process. Several recent studies have suggested that the efficiency of genome replication for poliovirus and other members of the Picornaviridæ family results from the recruitment of a phosphatidylinositol (PI) kinase, PI4KIIIβ (phosphatidylinositol-4-kinase IIIβ), which generates a lipid membrane microenvironment rich in PI4P (phosphatidylinositol-4-phosphate) at sites of replication. The nonstructural protein 3A of these viruses has been shown to play a role in the enrichment of replication organelle membranes in PI4KIIIβ, but the mechanisms of kinase recruitment seem to differ between members of this family of viruses. Hepatitis C, from the Flaviviridæ family, recruits another PI4KIII kinase, PI4KIIIα, to sites of replication, through another nonstructural protein, NS5A. In this review, we will describe the various recently proposed models and the potential role of PI4P lipids. Finally, we will show that PI4KIII kinases are potential targets for the development of antiviral drugs targeting many positive-polarity RNA viruses.