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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02186

Common Nodes of Virus–Host Interaction Revealed Through an Integrated Network Analysis

  • 1Centre of Molecular Inflammation Research, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Norway
  • 2Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Norway
  • 3Korea Pasteur Institute, South Korea
  • 4Department of Virology, Faculty of Medicine, University of Helsinki, Finland
  • 5Institute of Technology, Faculty of Science and Technology, University of Tartu, Estonia
  • 6Pauls Stradins Clinical university hospital, Latvia
  • 7Department of Laboratory Medicine, Faculty of Medicine, Lithuanian University of Health Science, Lithuania
  • 8Department of Clinical Sciences, University of Bergen, Norway
  • 9Department of Medical Sciences, Uppsala University, Sweden
  • 10Department of Microbiology, Oslo University Hospital, Norway
  • 11Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Finland
  • 12CeMM Research Center for Molecular Medicine (OAW), Austria
  • 13Center for Physiology and Pharmacology, Medical University of Vienna, Austria
  • 14Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, Switzerland
  • 15Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Norway
  • 16Centre for Molecular Medicine Norway, Faculty of Medicine, University of Oslo, Norway

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 signalling 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, human
metapneumovirus and Sindbis virus. 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: virus–host interaction, protein–protein interaction, innate immunity, viral evasion, Network analysis, gene–drug interaction, molecular innate immunity

Received: 04 Mar 2019; Accepted: 29 Aug 2019.

Copyright: © 2019 Bösl, Ianevski, Than, Andersen, Kuivanen, Teppor, Zusinaite, Dumpis, Vitkauskiene, Cox, Kallio-Kokko, Bergqvist, Tenson, Merits, Oksenych, Bjøras, 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.

* Correspondence: Prof. Richard Kumaran Kandasamy, Centre of Molecular Inflammation Research, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, NO-7491, Sør-Trøndelag, Norway, richard.k.kandasamy@ntnu.no