Functional interactomes of the Ebola virus polymerase identified by proximity proteomics in the context of viral replication.
Functional interactomes of the Ebola virus polymerase identified by proximity proteomics in the context of viral replication.
复制标题
在病毒复制的背景下，通过接近蛋白质组学鉴定的埃博拉病毒聚合酶的功能相互作用组。
DOI：
10.1016/j.celrep.2022.110544
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发表时间：
2022-03-22
期刊：
影响因子：
8.8
通讯作者：
Saphire, Erica Ollmann
中科院分区：
文献类型：
--
作者：
Fang, Jingru;Pietzsch, Colette;Tsaprailis, George;Crynen, Gogce;Cho, Kelvin Frank;Ting, Alice Y.;Bukreyev, Alexander;de la Torre, Juan Carlos;Saphire, Erica Ollmann
Ebola virus (EBOV) critically depends on the viral polymerase to replicate and transcribe the viral RNA genome in the cytoplasm of host cells, where cellular factors can antagonize or facilitate the virus life cycle. Here we leverage proximity proteomics and conduct a small interfering RNA (siRNA) screen to define the functional interactome of EBOV polymerase. As a proof of principle, we validate two cellular mRNA decay factors from 35 identified host factors: eukaryotic peptide chain release factor subunit 3a (eRF3a/GSPT1) and up-frameshift protein 1 (UPF1). Our data suggest that EBOV can subvert restrictions of cellular mRNA decay and repurpose GSPT1 and UPF1 to promote viral replication. Treating EBOV-infected human hepatocytes with a drug candidate that targets GSPT1 for degradation significantly reduces viral RNA load and particle production. Our work demonstrates the utility of proximity proteomics to capture the functional host interactome of the EBOV polymerase and to illuminate host-dependent regulation of viral RNA synthesis. Using proximity proteomics coupled with siRNA screens, Fang et al. reveal functional interactomes of the Ebola virus polymerase, which drives synthesis of viral RNA. These functional hits illuminate a panel of host-dependent regulators of Ebola viral RNA synthesis, which could be potential targets for antiviral drug discovery and development.
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影响因子：
8.8
作者：
Leung DW;Borek D;Luthra P;Binning JM;Anantpadma M;Liu G;Harvey IB;Su Z;Endlich-Frazier A;Pan J;Shabman RS;Chiu W;Davey RA;Otwinowski Z;Basler CF;Amarasinghe GK
通讯作者：
Amarasinghe GK
影响因子：
30.3
作者：
Hoffmann HH;Sánchez-Rivera FJ;Schneider WM;Luna JM;Soto-Feliciano YM;Ashbrook AW;Le Pen J;Leal AA;Ricardo-Lax I;Michailidis E;Hao Y;Stenzel AF;Peace A;Zuber J;Allis CD;Lowe SW;MacDonald MR;Poirier JT;Rice CM
通讯作者：
Rice CM
影响因子：
5.4
作者：
Hoenen, Thomas;Shabman, Reed S.;Feldmann, Heinz
通讯作者：
Feldmann, Heinz
影响因子：
4.4
作者：
Garcia-Dorival, Isabel;Wu, Weining;Hiscox, Julian A.
通讯作者：
Hiscox, Julian A.
影响因子：
5.4
作者：
Brauburger, Kristina;Boehmann, Yannik;Muehlberger, Elke
通讯作者：
Muehlberger, Elke