| Summary: | Oncoviruses rewire host pathways to subvert host immunity and promote their survival and proliferation. However, exactly how is challenging to understand. Here, by employing the first and to date only interface-based host-microbe interaction (HMI) prediction method, we explore a pivotal strategy oncoviruses use to drive cancer: mimicking binding surfaces—interfaces—of human proteins. We show that oncoviruses can target key human network proteins and transform cells by acquisition of cancer hallmarks. Experimental large-scale mapping of HMIs is difficult and individual HMIs do not permit in-depth grasp of tumorigenic virulence mechanisms. Our computational approach is tractable and 3D structural HMI models can help elucidate pathogenesis mechanisms and facilitate drug design. We observe that many host proteins are unique targets for certain oncoviruses, whereas others are common to several, suggesting similar infectious strategies. A rough estimation of our false discovery rate based on the tissue expression of oncovirus-targeted human proteins is 25%.
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