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

This unique dataset can be used for further detailed interrogation of the mechanisms behind viral evasion. This could serve as a starting point for identifying novel host targets and generating hypothesis in the context of viral evasion and development of pan-viral therapeutic intervention strategies. The methods described here also provide unique ways of dissecting the orthogonal datasets. Various analyses from this study have highlighted the existence on pan-viral evasion points that could be utilised for the development of host-directed antiviral therapies. It is also intriguing to see that there is commonality and specificity at the level of subcellular localization of the viral targets. Our analyses have underlined some salient features in the context of IAV, HPV, DENV and HCV. Further detailed analysis in this context along with protein sequence features, such as Short Linear Motifs (SLiMs) (Davey et al. 2011 ) would provide novel insights as well as deeper understanding of how small sequence features are involved in the hijacking of the host machinery. Integration of such data with known druggene interactions provides a clear estimate of the druggable proportion in the hvPPI. Our meta-analysis approach of the hvPPI could provide novel avenues of re-purposing existing drugs for antiviral targeting strategies.