Oncoviruses Can Drive Cancer by Rewiring Signaling Pathways Through Interface Mimicry

Emine Guven-Maiorov, Chung Jung Tsai, Ruth Nussinov*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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%.

Original languageEnglish
Article number1236
JournalFrontiers in Oncology
StatePublished - 15 Nov 2019


FundersFunder number
Center for Cancer Research
National Institutes
U.S. Government
National Institutes of HealthHHSN261200800001E
National Cancer Institute
Department of Health, Australian Government


    • computational prediction/modeling
    • host-microbe interaction
    • host-pathogen interaction
    • interface mimicry
    • pathogen-driven cancer
    • protein-protein interaction
    • structure
    • superorganism network


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