We will discuss the implication of the functional enrichment JNK inhibitor profile of the cellular proteins identified in our screen and how these proteins affect the virus replication and assembly. Table 4 Gene Ontology (GO) functional enrichment analysis of the flavivirus-targeted human proteins Ontology Description GO term p-value Associated
proteins Molecular function RNA binding GO:0003723 **** EIF5A, HNRPF, selleck inhibitor HNRPH3, ILF3, MATR3, MRPL20, PABPC1, PPRC1, PRKRA, RNUXA, RPS20, SSB, TAF15, TRIM21, SNRPA, XPO1, ZCCHC17 Structural constituent of cytoskeleton GO:0005200 ** ACTB, ACTG1, BICD1, KRT19, VIM Nuclear localization sequence binding GO:0008139 ** KPNB1, NFKBIA Transcription factor binding GO:0008134 * ARNTL, CAMTA2, HNRNPF, KAT5, MDF1, MED4, NFKBIA Transcription corepressor activity GO:0003714 * ATN1, ENO1, RNF12, SIAH2, TSG101 Cellular CH5424802 nmr component Cytoskeleton GO:0005856 **** ACTA2, ACTB, ACTG1, ACTG2, APBB1IP, AXIN1, BICD1, CASP8, CCDC99, CEP250, CEP290, CEP63, CHD3, CLIP1, DNM2, FHL2, GOPC, KIF3B, KRT19, LMNA, MLPH, MYH9, PDE4DIP, TRAF4, TYK2, VIM Ribonucleoprotein complex GO:0030529 ** ACTB, HNRNPF, HNRNPH3, ILF3, MRPL20, PABPC1, RPS20, SSB, SNRPA, ZCCHC17 H4/H2A histone acetyltransferase complex GO:0043189 ** ACTB, KAT5 Biological process Intracellular transport
GO:0046907 *** AXIN1, BICD1, DNM2, EIF5A, GGA1, GOPC, KIF3B, KPNB1, MLPH, NFKBIA, NRBP1, OPTN, RNUXA, TOM1L1, TSG101, XPO1 Regulation of type I interferon-mediated signaling pathway GO:0060338 *** HSP90AB1, IFNAR2, STAT2, TYK2 Regulation of innate immune response GO:0045088 ** HSP90AB1, IFNAR2, NFKBIA, TRAFD1, TYK2 Viral reproductive process GO:0022415 ** KPNB1, PPIA, RPS20, SMARCB1, TSG101, XPO1 Post-Golgi vesicle-mediated transport GO:0006892 * DNM2, GOPC, OPTN Nuclear transport GO:0051169 * AXIN1, EIF5A, KPNB1, NFKBIA, RNUXA We assigned their GO features to the human proteins identified
in our screen (literature plus Y2H). We then determined if these features were over-represented in comparison with the complete list of the annotated human proteins. The description of the GO enriched Cytidine deaminase term (column 2), the corresponding GO identifier (column 3), the significativity of the functional enrichment test (**** p-value < = 0.0001, *** p-value < = 0.001, ** p-value < = 0.01, * p-value < 0, 05) and the associated proteins (colum 5) are given in table 4. The three GO subcategories are presented: molecular function, cellular component and biological process. Inter-connection of the cellular proteins targeted by flaviviruses Only 1/3 of the cellular proteins are represented in the human-human protein-protein interactome, suggesting that most of the cellular proteins are not connected [19]. We observed that the human proteins targeted by the flavivirus NS3 and NS5 were highly overrepresented in the human interactome (108/120, exact Fisher test, p-value < 2, 2.10-16).