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Author(s): Andreas Pichlmair [sup.1] [sup.2] , Kumaran Kandasamy [sup.1] , Gualtiero Alvisi [sup.3] , Orla Mulhern [sup.4] , Roberto Sacco [sup.1] , Matthias Habjan [sup.2] [sup.5] , Marco Binder [sup.3] [...], A systems approach provides a global perspective of the different strategies that viruses use to modulate the cellular innate immune response; this may be useful in the design of future viral intervention strategies. How viruses target innate immunity Andreas Pichlmair et al. take a systems approach to obtain a global perspective of the different strategies that viruses use to modulate the cellular innate immune response. The results demonstrate that viruses have evolved to exploit a variety of cellular mechanisms, and suggest that the host cell relies on homeostatic regulation across these diverse cellular processes to defend itself against pathogen interference. A central goal of this work is to identify common targets and general network properties in the host antiviral defence system that may be useful in the design of future viral-intervention strategies. 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.sup.1,2. Many viral open reading frames (viORFs) with immune-modulating functions essential for productive viral growth have been identified across a range of viral classes.sup.3,4. 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.sup.5,6,7,8,9,10,11. 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.

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 [...]

Regulation of Inducible and Tissue-Specific Gene Expression ACENTRAL PROBLEM IN EUKARYOTIC MOLECULAR BIOLOGYis to understand the mechanisms by which specific genes are expressed in a temporal or tissue-specific manner or [...]

A study shows that the classical signal-transduction pathway could be ignored totally by the events started by occupation of the Notch receptor. Study of the Notch gene is of great interest to biologists as the gene plays an important role in lateral specification, a process in which a cell differentiates. Cells in the ectodermal monolayer turn into neuronal-like tissue due to null mutations in Notch. A study is conducted on rats to understand the Notch signalling pathway.