UMMS Affiliation

Program in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine

Publication Date

2019-10-04

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Bioinformatics | Genetic Phenomena | Hemic and Immune Systems | Immunity | Immunology of Infectious Disease | Integrative Biology | Nucleic Acids, Nucleotides, and Nucleosides | Virology | Viruses

Abstract

Viruses are one of the major causes of acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to hijack basic cellular pathways and evade innate immune response by modulating key host factors and signaling pathways. A collective view of these multiple studies could advance our understanding of virus-host interactions and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve the maximal effect by targeting multifunctional and highly connected host proteins with a high occurrence of disordered regions. We also identified the core cellular process subnetworks that are targeted by all the viruses. Integration with functional RNA interference (RNAi) datasets showed that a large proportion of the targets are required for viral replication. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Altogether, these orthogonal datasets could serve as a platform for hypothesis generation and follow-up studies to broaden our understanding of the viral evasion landscape.

Keywords

gene–drug interaction, innate immunity, molecular innate immunity, network analysis, protein–protein interaction, viral evasion, virus–host interaction

Rights and Permissions

Copyright © 2019 Bösl, Ianevski, Than, Andersen, Kuivanen, Teppor, Zusinaite, Dumpis, Vitkauskiene, Cox, Kallio-Kokko, Bergqvist, Tenson, Merits, Oksenych, Bjørås, Anthonsen, Shum, Kaarbø, Vapalahti, Windisch, Superti-Furga, Snijder, Kainov and Kandasamy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

DOI of Published Version

10.3389/fimmu.2019.02186

Source

Front Immunol. 2019 Oct 4;10:2186. doi: 10.3389/fimmu.2019.02186. eCollection 2019. Link to article on publisher's site

Journal/Book/Conference Title

Frontiers in immunology

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

31636628

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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