Viral immune modulators perturb the human molecular network by common and unique strategies View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2012-07

AUTHORS

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

ABSTRACT

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. More... »

PAGES

486

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature11289

DOI

http://dx.doi.org/10.1038/nature11289

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1031504493

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22810585


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