Chikungunya virus(CHIKV)is a re-emerging mosquito-transmitted RNA virus causing joint and muscle pain.To better understand how CHIKV rewires the host cell and usurps host cell functions,we generated a systematic CHIKV...Chikungunya virus(CHIKV)is a re-emerging mosquito-transmitted RNA virus causing joint and muscle pain.To better understand how CHIKV rewires the host cell and usurps host cell functions,we generated a systematic CHIKV-human protein-protein interaction map and revealed several novel connections that will inform further mechanistic studies.One of these novel interactions,between the viral protein E1 and STIP1 homology and U-box containing protein 1(STUB1),was found to mediate ubiquitination of E1 and degrade E1 through the proteasome.Capsid associated with G3BP1,G3BP2 and AAAþATPase valosin-containing protein(VCP).Furthermore,VCP inhibitors blocked CHIKV infection,suggesting VCP could serve as a therapeutic target.Further work is required to fully understand the functional consequences of these interactions.Given that CHIKV proteins are conserved across alphaviruses,many virus-host protein-protein interactions identified in this study might also exist in other alphaviruses.Construction of interactome of CHIKV provides the basis for further studying the function of alphavirus biology.展开更多
基金supported by National Natural Science Foundation of China (82072270 and 82272306)Taishan Scholars Program (tstp20221142)+1 种基金Shandong Provincial Natural Science Foundation (ZR2021QC095)Academic Promotion Programme of Shandong First Medical University (2019LJ001).
文摘Chikungunya virus(CHIKV)is a re-emerging mosquito-transmitted RNA virus causing joint and muscle pain.To better understand how CHIKV rewires the host cell and usurps host cell functions,we generated a systematic CHIKV-human protein-protein interaction map and revealed several novel connections that will inform further mechanistic studies.One of these novel interactions,between the viral protein E1 and STIP1 homology and U-box containing protein 1(STUB1),was found to mediate ubiquitination of E1 and degrade E1 through the proteasome.Capsid associated with G3BP1,G3BP2 and AAAþATPase valosin-containing protein(VCP).Furthermore,VCP inhibitors blocked CHIKV infection,suggesting VCP could serve as a therapeutic target.Further work is required to fully understand the functional consequences of these interactions.Given that CHIKV proteins are conserved across alphaviruses,many virus-host protein-protein interactions identified in this study might also exist in other alphaviruses.Construction of interactome of CHIKV provides the basis for further studying the function of alphavirus biology.
