Gene interactions and pathways from curated databases and text-mining
Nature 2012, PMID: 22810585

Viral immune modulators perturb the human molecular network by common and unique strategies.

Pichlmair, Andreas; Kandasamy, Kumaran; Alvisi, Gualtiero; Mulhern, Orla; Sacco, Roberto; Habjan, Matthias; Binder, Marco; Stefanovic, Adrijana; Eberle, Carol-Ann; Goncalves, Adriana; Bürckstümmer, Tilmann; Müller, André C; Fauster, Astrid; Holze, Cathleen; Lindsten, Kristina; Goodbourn, Stephen; Kochs, Georg; Weber, Friedemann; Bartenschlager, Ralf; Bowie, Andrew G; Bennett, Keiryn L; Colinge, Jacques; Superti-Furga, Giulio

Viruses must enter host cells to replicate, assemble and propagate. Because of the restricted size of their genomes, viruses have had to evolve efficient ways of exploiting host cell processes to promote their own life cycles and also to escape host immune defence mechanisms. Many viral open reading frames (viORFs) with immune-modulating functions essential for productive viral growth have been identified across a range of viral classes. However, there has been no comprehensive study to identify the host factors with which these viORFs interact for a global perspective of viral perturbation strategies. Here we show that different viral perturbation patterns of the host molecular defence network can be deduced from a mass-spectrometry-based host-factor survey in a defined human cellular system by using 70 innate immune-modulating viORFs from 30 viral species. The 579 host proteins targeted by the viORFs mapped to an unexpectedly large number of signalling pathways and cellular processes, suggesting yet unknown mechanisms of antiviral immunity. We further experimentally verified the targets heterogeneous nuclear ribonucleoprotein U, phosphatidylinositol-3-OH kinase, the WNK (with-no-lysine) kinase family and USP19 (ubiquitin-specific peptidase 19) as vulnerable nodes in the host cellular defence system. Evaluation of the impact of viral immune modulators on the host molecular network revealed perturbation strategies used by individual viruses and by viral classes. Our data are also valuable for the design of broad and specific antiviral therapies.

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Text Mining Data

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Manually curated Databases

  • IRef Intact Interaction: Complex of 11 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of DDB1-DDA1-CUL4A (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 43 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of EP300-CREBBP (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of PIK3R2-PCID2-IRS4 (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of PIK3R2-HSPA1L-IRS4 (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 39 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 16 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 22 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of STAT2-NEFH-HSPA1L (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of TUBA1C-SPRR1B-HSPA5-SPRR1A-TUBA1A-PRDX1-S100A7-PPP2R1A (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 27 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 30 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 50 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of TUBA1A-TUBA1C-NUDT21-CPSF6 (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of STAT1-PPP2R2A (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of KIF3C-TUBB-TRIM21-BAG2-LGALS3BP-EIF4H (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 81 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of HIST1H1A-TCEB1-ZSWIM8-TRIM56-TCEB2-HIST1H1T-NEFH (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 73 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 12 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of NEFH-ACAP2 (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 22 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 15 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 11 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of RPL23-TUBA1C-TUBB-SLC25A5-RBM14-SLC25A4-TUBA1A-CCAR2-SLC25A6 (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 90 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 23 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of VPS26B-HSPA1L-VPS35 (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 43 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 17 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 16 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of DYNLL2-KPNA3-RPS17-HSPA5-CSNK2A1-ZMYND11-CSNK2B-DYNLL1 (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 18 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 34 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of ACTBL2-HIST1H1T-HIST1H1A-GTF2B-CAPN15 (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 83 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of NEFH-USP7 (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 22 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 15 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of STUB1-HIST1H1T-HIST1H1A-TP53-BAG2-HSPA2 (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 11 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 13 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 14 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 39 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of TCEB2-TRIM56-ZSWIM8 (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 31 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 20 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 64 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of PIK3R2-IRS4-DHX9-HNRNPR-SYNCRIP (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of TCEB2-HIST1H1A-TRIM56-TCEB1-HIST1H1T-ZSWIM8 (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 35 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 20 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 48 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 111 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 25 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of TUBA1A-RPS18-MAP4K4-TSG101-VPS37B-VPS28-MVB12A-MVB12B-TUBA1C (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of STAT1-STAT2-HIST1H1A-HIST1H1T (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 50 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 57 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 35 proteins (association, tandem affinity purification)
  • IRef Intact Interaction: Complex of 32 proteins (association, tandem affinity purification)
In total, 23836 gene pairs are associated to this article in curated databases