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Common Nodes of Virus-Host Interaction Revealed Through an Integrated Network Analysis
Norwegian Univ Sci & Technol, Ctr Mol Inflammat Res, Trondheim, Norway;Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
Inst Pasteur Korea, Seongnam, South Korea.
Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
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2019 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, article id 2186Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA , 2019. Vol. 10, article id 2186
Keywords [en]
virus-host interaction, protein-protein interaction, gene-drug interaction, innate immunity, viral evasion, network analysis, molecular innate immunity
National Category
Immunology
Identifiers
URN: urn:nbn:se:uu:diva-398032DOI: 10.3389/fimmu.2019.02186ISI: 000496975700001PubMedID: 31636628OAI: oai:DiVA.org:uu-398032DiVA, id: diva2:1375074
Funder
The Research Council of Norway, 263168The Research Council of Norway, 223255/F50Available from: 2019-12-04 Created: 2019-12-04 Last updated: 2019-12-04Bibliographically approved

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