Qian Xijing, Xu Chen, Zhao Ping, Qi Zhongtian
Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, 800th Xiangyin Road, Shanghai 200433, PR China.
Department of Orthopedics, Changzheng Hospital Affiliated to Second Military Medical University, 415th Feng Yang Road, Shanghai 200003, PR China.
Virology. 2016 May;492:155-65. doi: 10.1016/j.virol.2016.02.020. Epub 2016 Mar 21.
HCV infection has a complex and dynamic process which involves a large number of viral and host factors. Long non-coding RNA GAS5 inhibits liver fibrosis and liver tumor migration and invasion. However, the contribution of GAS5 on HCV infection remains unknown. In this study, GAS5 was gradually upregulated during HCV infection in Huh7 cells. In addition, GAS5 attenuated virus replication with its 5' end sequences, as confirmed by different GAS5 truncations. Moreover, this 5' end sequences showed RNA-protein interaction with HCV NS3 protein that could act as a decoy to inhibit its functions, which contributed to the suppression of HCV replication. Finally, the innate immune responses remained low in HCV infected Huh7 cells, ruling out the possibility of GAS5 to modulate innate immunity. Thus, HCV stimulated endogenous GAS5 can suppress HCV infection by acting as HCV NS3 protein decoy, providing a potential role of GAS5 as a diagnostic or therapeutic target.
丙型肝炎病毒（HCV）感染是一个复杂且动态的过程，涉及大量病毒和宿主因素。长链非编码RNA GAS5可抑制肝纤维化以及肝脏肿瘤的迁移和侵袭。然而，GAS5在HCV感染中的作用尚不清楚。在本研究中，Huh7细胞感染HCV期间，GAS5表达逐渐上调。此外，不同的GAS5截短体证实，GAS5的5'端序列可减弱病毒复制。而且，该5'端序列显示与HCV NS3蛋白存在RNA-蛋白质相互作用，可作为诱饵抑制其功能，从而抑制HCV复制。最后，HCV感染的Huh7细胞中固有免疫反应仍然较低，排除了GAS5调节固有免疫的可能性。因此，HCV刺激产生的内源性GAS5可作为HCV NS3蛋白的诱饵抑制HCV感染，提示GAS5可能具有作为诊断或治疗靶点的潜在作用。
