Comparative influenza protein interactomes identify the role of plakophilin 2 in virus restriction

作者：Lingyan Wang, Bishi Fu, Wenjun Li, Girish Patil, Lin Liu, Martin E. Dorf, Shitao Li · 发表于：Nature Communications · 年份：2017 · DOI：10.1038/ncomms13876 · 被引用次数：84 · 研究领域：Influenza Virus Research Studies、RNA and protein synthesis mechanisms、interferon and immune responses

Cellular protein interaction networks are integral to host defence and immune signalling pathways, which are often hijacked by viruses via protein interactions. However, the comparative virus-host protein interaction networks and how these networks control host immunity and viral infection remain to be elucidated. Here, we mapped protein interactomes between human host and several influenza A viruses (IAV). Comparative analyses of the interactomes identified common and unique interaction patterns regulating innate immunity and viral infection. Functional screening of the 'core' interactome consisting of common interactions identified five novel host factors regulating viral infection. Plakophilin 2 (PKP2), an influenza PB1-interacting protein, restricts IAV replication and competes with PB2 for PB1 binding. The binding competition leads to perturbation of the IAV polymerase complex, thereby limiting polymerase activity and subsequent viral replication. Taken together, comparative analyses of the influenza-host protein interactomes identified PKP2 as a natural inhibitor of IAV polymerase complex.