Comparative interactomics for virus-human protein-protein interactions: DNA viruses versus RNA viruses

Abstract

Viruses are obligatory intracellular pathogens and completely depend on their hosts for survival and reproduction. The strategies adopted by viruses to exploit host cell processes and to evade host immune systems during infections may differ largely with the type of the viral genetic material. An improved understanding of these viral infection mechanisms is only possible through a better understanding of the pathogen-host interactions (PHIs) that enable viruses to enter into the host cells and manipulate the cellular mechanisms to their own advantage. Experimentally-verified protein-protein interaction (PPI) data of pathogen-host systems only became available at large scale within the last decade. In this study, we comparatively analyzed the current PHI networks belonging to DNA and RNA viruses and their human host, to get insights into the infection strategies used by these viral groups. We investigated the functional properties of human proteins in the PHI networks, to observe and compare the attack strategies of DNA and RNA viruses. We observed that DNA viruses are able to attack both human cellular and metabolic processes simultaneously during infections. On the other hand, RNA viruses preferentially interact with human proteins functioning in specific cellular processes as well as in intracellular transport and localization within the cell. Observing virus-targeted human proteins, we propose heterogeneous nuclear ribonucleoproteins and transporter proteins as potential antiviral therapeutic targets. The observed common and specific infection mechanisms in terms of viral strategies to attack human proteins may provide crucial information for further design of broad and specific next-generation antiviral therapeutics.

Keywords: DNA virus; RNA virus; comparative interactomics; next‐generation antiviral therapeutics; pathogen–host interaction; viral infection strategy.

Figure 1

Virus–human PHI networks obtained from phisto. Red nodes are viral proteins and blue nodes are human proteins. (A) Human herpesvirus 4 (Epstein–Barr virus) – human protein–protein interaction network. (B) Influenza A virus strain WSN/1933/TS61 (H1N1) – human protein–protein interaction network.