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.

Virological and Immunological Outcomes of Coinfections

“…In an infected cell, viruses can interact with a large number of cellular proteins (virus-host interactome) that may either support or inhibit virus replication. As with virus-host protein interactions, protein-protein interactions between unrelated viruses are also possible (6,7). Coinfections may result in genetic exchange between agents to generate recombinant viruses.…”

Structural Genomics of SARS-CoV-2 Indicates Evolutionary Conserved Functional Regions of Viral Proteins

“…In particular, a plethora of results has been achieved through comparative, or homology, modeling principles [32,33]. In addition to the global structural genomics, an initiative that focuses on determining the 3D structures of individual proteins on a genome scale [34], as well as to the specific efforts aimed at rapid structural characterization of proteins in emerging viruses [35][36][37][38], multiple works have used comparative modeling to predict the structures of protein-protein interaction complexes [39][40][41], facilitate structure-based drug discovery [33,42,43], infer protein functions [44], determine the macromolecular interaction network [45][46][47][48], and provide molecular insights into the viral evolution [49][50][51].…”

Structural genomics and interactomics of 2019 Wuhan novel coronavirus, 2019-nCoV, indicate evolutionary conserved functional regions of viral proteins

“…In particular, a plethora of results has been achieved through comparative, or homology, modeling principles [32,33]. In addition to the global structural genomics initiatives focusing on determining the 3D structures of proteins on a genome scale [34] and specific efforts on rapid structural characterization of proteins in emerging viruses [35][36][37][38], multiple works have used comparative modeling to predict the structures of protein-protein interaction complexes [39][40][41], facilitating structure-based drug discovery [33,42,43], inferring protein functions [44], determining the macromolecular interaction network [45][46][47], and providing molecular insights into viral evolution [48][49][50].…”