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Front Immunol. 2019 Oct 4;10:2186. doi: 10.3389/fimmu.2019.02186. eCollection 2019. Common Nodes of Virus-Host Interaction Revealed Through an Integrated Network Analysis.
B?sl K1,2, Ianevski A2, Than TT3, Andersen PI2, Kuivanen S4, Teppor M5, Zusinaite E5, Dumpis U6, Vitkauskiene A7, Cox RJ8, Kallio-Kokko H9, Bergqvist A10, Tenson T5, Merits A5, Oksenych V2, Bj?r?s M2, Anthonsen MW2, Shum D3, Kaarb? M11, Vapalahti O12, Windisch MP3, Superti-Furga G13,14, Snijder B15, Kainov D2,5, Kandasamy RK1,2,16,17.
Author information
1 Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway. 2 Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. 3 Institut Pasteur Korea, Seongnam, South Korea. 4 Department of Virology, University of Helsinki, Helsinki, Finland. 5 Institute of Technology, University of Tartu, Tartu, Estonia. 6 Pauls Stradins Clinical University Hospital, Riga, Latvia. 7 Department of Laboratory Medicine, Lithuanian University of Health Science, Kaunas, Lithuania. 8 Department of Clinical Science, Influenza Centre, University of Bergen, Bergen, Norway. 9 Department of Virology and Immunology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland. 10 Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 11 Department of Microbiology, Oslo University Hospital, Oslo, Norway. 12 Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland. 13 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. 14 Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria. 15 Department of Biology, Institute of Molecular Systems Biology, ETH Z?rich, Zurich, Switzerland. 16 Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway. 17 Program in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, United States.
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.
Copyright ? 2019 B?sl, Ianevski, Than, Andersen, Kuivanen, Teppor, Zusinaite, Dumpis, Vitkauskiene, Cox, Kallio-Kokko, Bergqvist, Tenson, Merits, Oksenych, Bj?r?s, Anthonsen, Shum, Kaarb?, Vapalahti, Windisch, Superti-Furga, Snijder, Kainov and Kandasamy.
KEYWORDS:
gene–drug interaction; innate immunity; molecular innate immunity; network analysis; protein–protein interaction; viral evasion; virus–host interaction
PMID: 31636628 PMCID: PMC6787150 DOI: 10.3389/fimmu.2019.02186
Free PMC Article