Frontiers in Immunology (Oct 2019)
Common Nodes of Virus–Host Interaction Revealed Through an Integrated Network Analysis
- Korbinian Bösl,
- Korbinian Bösl,
- Aleksandr Ianevski,
- Thoa T. Than,
- Petter I. Andersen,
- Suvi Kuivanen,
- Mona Teppor,
- Eva Zusinaite,
- Uga Dumpis,
- Astra Vitkauskiene,
- Rebecca J. Cox,
- Hannimari Kallio-Kokko,
- Anders Bergqvist,
- Tanel Tenson,
- Andres Merits,
- Valentyn Oksenych,
- Magnar Bjørås,
- Marit W. Anthonsen,
- David Shum,
- Mari Kaarbø,
- Olli Vapalahti,
- Marc P. Windisch,
- Giulio Superti-Furga,
- Giulio Superti-Furga,
- Berend Snijder,
- Denis Kainov,
- Denis Kainov,
- Richard K. Kandasamy,
- Richard K. Kandasamy,
- Richard K. Kandasamy,
- Richard K. Kandasamy
Affiliations
- Korbinian Bösl
- Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway
- Korbinian Bösl
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- Aleksandr Ianevski
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- Thoa T. Than
- Institut Pasteur Korea, Seongnam, South Korea
- Petter I. Andersen
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- Suvi Kuivanen
- Department of Virology, University of Helsinki, Helsinki, Finland
- Mona Teppor
- Institute of Technology, University of Tartu, Tartu, Estonia
- Eva Zusinaite
- Institute of Technology, University of Tartu, Tartu, Estonia
- Uga Dumpis
- Pauls Stradins Clinical University Hospital, Riga, Latvia
- Astra Vitkauskiene
- Department of Laboratory Medicine, Lithuanian University of Health Science, Kaunas, Lithuania
- Rebecca J. Cox
- Department of Clinical Science, Influenza Centre, University of Bergen, Bergen, Norway
- Hannimari Kallio-Kokko
- Department of Virology and Immunology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland
- Anders Bergqvist
- 0Department of Medical Sciences, Uppsala University, Uppsala, Sweden
- Tanel Tenson
- Institute of Technology, University of Tartu, Tartu, Estonia
- Andres Merits
- Institute of Technology, University of Tartu, Tartu, Estonia
- Valentyn Oksenych
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- Magnar Bjørås
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- Marit W. Anthonsen
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- David Shum
- Institut Pasteur Korea, Seongnam, South Korea
- Mari Kaarbø
- 1Department of Microbiology, Oslo University Hospital, Oslo, Norway
- Olli Vapalahti
- 2Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland
- Marc P. Windisch
- Institut Pasteur Korea, Seongnam, South Korea
- Giulio Superti-Furga
- 3CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
- Giulio Superti-Furga
- 4Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria
- Berend Snijder
- 5Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zurich, Switzerland
- Denis Kainov
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- Denis Kainov
- Institute of Technology, University of Tartu, Tartu, Estonia
- Richard K. Kandasamy
- Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway
- Richard K. Kandasamy
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- Richard K. Kandasamy
- 6Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway
- Richard K. Kandasamy
- 7Program in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, United States
- DOI
- https://doi.org/10.3389/fimmu.2019.02186
- Journal volume & issue
-
Vol. 10
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
- virus–host interaction
- protein–protein interaction
- gene–drug interaction
- innate immunity
- viral evasion
- network analysis
