Indeed, even though DENV-2 NS5 contains two functional NLS which were shown to interact with the importin and the exportin proteins, KPNB1 and XPO1 [28, 29], the role of NS5 in the nucleus has not yet been elucidated [6]. The NS3 and NS5 proteins were also found to interact with several proteins belonging to the cell RNA processing machinery

such as HNRPF, PABPC1 or HNRPH3. These results are in accordance with the recent identification of non-polyadenylated 3′ end of dengue virus RNA as a viral partner for PABPC1 [30] and emphasize the possible cooperation between viral and human proteins during viral genome replication. A common feature observed in a large number of viruses is their ability to disorganize the cytoskeleton by targeting central component of the microtubule, intermediate or micro-filament system networks. In this GSK2118436 price regard, our data are in accordance with a genome-scale RNAi screen which revealed that silencing genes involved in intracellular trafficking affects the outcome of a WNV infection [16]. However,

our work not only demonstrates that flavivirus proteins interact with cytoskeleton components known to be targeted by other viruses but also identifies new host protein targets involved in intracellular trafficking. These include in particular the kinesin family member KIF3B and the centrosomal components CEP63, CEP250 and CEP290. ACTB and VIM appear as central “”hubs”" in the highly connected flavivirus-human protein network suggesting they may be key components of viral particle production. Supporting this view, dengue virus production has already been associated with vimentin filament perturbation selleck chemicals [31]. Besides proteins involved in cytoskeleton network, we also identified a smaller sub-network composed of three proteins belonging to the post-Golgi vesicular transport (TOM1L1, TSG101 and GGA1) and four proteins associated with the Golgi vesicle transport (DNM2, GOPC, NRBP1, OPTN). These proteins are most likely involved in the virus-induced membrane rearrangements associated to DENV replication and assembly in the so-called replication factories [7, 32]. Conclusion In conclusion,

we JPH203 cell line report here the results of a proteome mapping screen to identify the interactions between human host proteins and the flavivirus NS3 and NS5 proteins. Our high-throughput yeast two-hybrid screen identified 108 human proteins interacting with Rebamipide NS3 or NS5 proteins or both. And our virus-host interaction map provides a foundation to unravel fundamental processes about flavivirus subversion of the host replication machinery and/or the immune defence strategy of the host. Acknowledgements and Funding We thank Dali Ma, Isabel Pombo-Grégoire and Serge Nataf for critical reading of the manuscript and helpful discussions. We also thank all the members of the I-MAP team for their continual support. The plasmids were produced as part of the European Virus Archive (EVA) project (European FP7 Capacities Project no 228292, http://​www.