Barriocanal Marina, Fortes Puri
Department of Gene Therapy and Hepatology, Navarra Institute for Health Research (IdiSNA), Centro de Investigación Médica Aplicada, University of Navarra, Pamplona, Spain.
Front Microbiol. 2017 Sep 28;8:1833. doi: 10.3389/fmicb.2017.01833. eCollection 2017.
Hepatitis C virus (HCV) often leads to a chronic infection in the liver that may progress to steatosis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Several viral and cellular factors are required for a productive infection and for the development of liver disease. Some of these are long non-coding RNAs (lncRNAs) deregulated in infected cells. After HCV infection, the sequence and the structure of the viral RNA genome are sensed to activate interferon (IFN) synthesis and signaling pathways. These antiviral pathways regulate transcription of several cellular lncRNAs. Some of these are also deregulated in response to viral replication. Certain viral proteins and/or viral replication can activate transcription factors such as MYC, SP1, NRF2, or HIF1α that modulate the expression of additional cellular lncRNAs. Interestingly, several lncRNAs deregulated in HCV-infected cells described so far play proviral or antiviral functions by acting as positive or negative regulators of the IFN system, while others help in the development of liver cirrhosis and HCC. The study of the structure and mechanism of action of these lncRNAs may aid in the development of novel strategies to treat infectious and immune pathologies and liver diseases such as cirrhosis and HCC.
丙型肝炎病毒(HCV)常常导致肝脏慢性感染,这种感染可能会发展为脂肪变性、纤维化、肝硬化和肝细胞癌(HCC)。有效的感染以及肝病的发展需要多种病毒和细胞因子。其中一些是在受感染细胞中失调的长链非编码RNA(lncRNA)。HCV感染后,病毒RNA基因组的序列和结构会被感知,从而激活干扰素(IFN)合成和信号通路。这些抗病毒通路调节多种细胞lncRNA的转录。其中一些lncRNA也会因病毒复制而失调。某些病毒蛋白和/或病毒复制可激活转录因子,如MYC、SP1、NRF2或HIF1α,这些转录因子会调节其他细胞lncRNA的表达。有趣的是,到目前为止,在HCV感染细胞中失调的几种lncRNA通过作为IFN系统的正调控因子或负调控因子发挥病毒前体或抗病毒功能,而其他lncRNA则有助于肝硬化和HCC的发展。对这些lncRNA的结构和作用机制的研究可能有助于开发治疗感染性和免疫性疾病以及肝硬化和HCC等肝病的新策略。