Cellular protein GLTSCR2: A valuable target for the development of broad-spectrum antivirals.

Cellular protein GLTSCR2: A valuable target for the development of broad-spectrum antivirals.
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细胞蛋白 GLTSCR2:开发广谱抗病毒药物的重要靶点

DOI:
10.1016/j.antiviral.2017.03.004
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发表时间:
2017-06
期刊:
影响因子:
7.6
通讯作者:
Wang XJ
Wang XJ
中科院分区:
医学2区
文献类型:
--
作者:
Li CC;Dong HJ;Wang P;Meng W;Chi XJ;Han SC;Ning S;Wang C;Wang XJ

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Viral infection induces translocation of the nucleolar protein GLTSCR2 from the nucleus to the cytoplasm, resulting in attenuation of the type I interferon IFN-β. Addressing the role of GLTSCR2 in viral replication, we detect that knocking down GLTSCR2 by shRNAs results in significant suppression of viral replication in mammalian and chicken cells. Injection of chicken embryo with the GLTSCR2-specific shRNA-1370 simultaneously or 24 h prior to infection with Newcastle disease virus (NDV) substantially reduces viral replication in chicken embryo fibroblasts. Injection of shRNA-1370 into chicken embryo also reduces the replication of avian influenza virus (AIV). In contrast, GLTSCR2-derived protein G4-T, forming α-helical dimers, increases replication of seven various DNA and RNA viruses in cells. Our studies reveal that alteration of the function of cellular GLTSCR2 plays a role in supporting viral replication. GLTSCR2 should be seriously considered as a therapeutic target for developing broad spectrum antiviral agents to effectively control viral infection. G4-T, a protein that mimics GLTSCR2, folds in an α-helical dimer structure. G4-T suppresses type I IFN antiviral response. G4-T promotes efficient proliferation of DNA and RNA viruses belonging to 7 families. GLTSCR2-specific shRNA reduces the infection of viruses in mammalian and chicken cells. Injection of GLTSCR2-specific shRNA into chicken embryo reduces the replication of NDV and AIV.
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