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

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; Valentyn Oksenych; Magnar Bjørås; Marit W. Anthonsen; David Shum; Mari Kaarbø; Olli Vapalahti; Marc P. Windisch; Giulio Superti-Furga; Berend Snijder; Denis Kainov; Richard K. Kandasamy

Viruses have evolved to evade the host antiviral response at various stages starting from viral sensing to antiviral pro-inflammatory responses (Bowie and Unterholzner 2008 , Navratil et al. 2011 , Garcia-Sastre 2017 . Multiple studies attempted to understand global principles of the viral evasion employed by various viruses, including dengue virus (DENV), Ebola virus (EBOV), IAV and HIV (Pichlmair et al. 2012 , Rozenblatt-Rosen et al. 2012 , Jäger et al. 2011 , Shah et al. 2018 , Batra et al. 2018 , Söderholm et al. 2016 . Global systems-level approaches including functional RNAi screens, interactome mapping technologies such as affinitypreprint purification mass spectrometry (AP-MS), quantitative proteomics and CRISPR/Cas9-based screens have provided unparalleled details and insights into the dynamics of host proteome in immune cells (Weekes et al. 2014 , Nightingale et al. 2018 , Kandasamy et al. 2016 , Ersing et al. 2017 ), host-virus interactome (Pichlmair et al. 2012 , Rozenblatt-Rosen et al. 2012 , Jäger et al. 2011 , Shapira et al. 2009 , Konig et al. 2010 , and also identified important host dependency factors of various viruses (Shapira et al. 2009 , Marceau et al. 2016 . Meta-analyses of such high-dimensional datasets have been crucial for identifying novel host factors as drug targets such as UBR4 in IAV infection (Tripathi et al. 2015) . Moreover, some of these factors represent drug targets for multiple viruses (Ianevski et al. 2018) .