Additional file 1:

Description of all the viral baits used in the Y2H screen. The viral baits are identified by their ViralORFeome identifier (column 2) and their associated GenBank protein identifier (column 3). Length, coordinates in the coding sequence and mutations are listed in ViralORFeome database http://www.viralorfeome.com webcite.

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Additional file 2:

The NS3 helicases sequences identity and similarity. For each protein pair, an alignment was performed and the protein sequence identity (blue) and similarity (black) percentage were given. Bold values represent high values of identities or similarities.

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Additional file 3:

List of the human proteins identified as flavivirus NS3 or NS5 targets. Flavivirus NS3- or NS5-targeted human proteins are referenced by their HGNC symbol (column 1) and their Ensembl Gene ID (column 2), their Ensembl description (column 3) and their source: Y2H screen (column 4) and/or literature (column 5).

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Additional file 4:

Validation of three Y2H interactions showing that DENV 2 NS3 interacts with some proteins involved in the innate immune response. HEK-293T cells were co-transfected with expression vectors encoding the GST alone or the GST fused to DENV2 NS3 helicase, and 3xFlag tagged TRAF4, NFKBIA or AZI2. Co-purifications were obtained by pull-down on total cell lysates. GST-tagged viral NS3 proteins were detected by immuno-blotting using anti-GST antibody, while TRAF4, NFKNIA or AZI2 were detected with anti-Flag antibodies before (lower panel, cell lysate) and after pull-down (upper panel, pull down).

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Additional file 5:

Human host-flavivirus NS3 and NS5 protein-protein interactions, functional domains specification. Human proteins are referenced by their HGNC symbol (column 1) and their Ensembl Gene ID (column 2), and the characteristics of the viral proteins are reported in column 3. The origin of the interaction is indicated in column 4 (Y2H screens) and/or 5 (literature).

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Additional file 6:

Degree and betweenness distributions. Degree (left) and betweenness [29] distributions of human proteins (black) and human proteins targeted by flavivirus proteins (red) in the human interactome. P(k) is the probability of a node to connect k other nodes in the network. P(b) is the probability of a node to have a betweeness equal to b in the network. Solid lines represent the linear regressions. Vertical dashed lines give mean degree and betweenness values.

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Additional file 7:

Flavivirus-targeted human proteins interactions with other viral proteins. Human proteins are referenced with their Ensembl Gene ID (column 1) and their HGNC symbol (column 2), viral proteins with their virus name (column 3), their NCBI id (column 4) and their NCBI name (column 5). These data were collected from the VirHostNet knowledge base.

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Additional file 8:

Statistical analysis of the interconnectivity of the human interactors of NS3 and NS5. Numbers distribution of protein-protein interactions was obtained by random simulation. 108 genes were randomly drawn from the genome 10, 000 times, and the 10, 000 numbers of protein-protein interactions in the subgraph existing between theses genes were plotted. A vertical arrow indicates the observed value of 84 interactions with its significance.

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