Hepatitis C, innate immunity and alcohol: friends or foes?
Hepatitis C, innate immunity and alcohol: friends or foes?
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DOI：
10.3390/biom5010076
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发表时间：
2015-02-05
期刊：
影响因子：
5.5
通讯作者：
Kharbanda KK
中科院分区：
文献类型：
--
作者：
Osna NA;Ganesan M;Kharbanda KK
丙型肝炎和酒精是世界范围内最普遍的肝病原因。大约80%有丙型肝炎和酒精滥用史的患者会发展为慢性肝损伤。丙型肝炎病毒（HCV）感染患者饮酒会加重肝脏疾病，导致纤维化、肝硬化甚至肝细胞癌的快速进展。肝细胞是HCV感染和乙醇代谢的主要场所，两者都产生氧化应激。氧化应激水平影响HCV复制和先天免疫，导致酒精中毒患者对HCV感染和病毒传播的易感性增加。在这篇综述中，我们分析了乙醇代谢和其他因素对HCV复制的影响。此外，我们还阐明了HCV如何劫持先天免疫以及乙醇暴露如何调节这一过程的机制。我们还阐明了HCV和乙醇代谢对干扰素信号传导的影响-激活抗病毒基因以保护细胞免受病毒侵害的关键点-以及HCV和乙醇诱导的损伤在适应性免疫中发挥的作用，这对于识别病毒感染的肝细胞是必要的。总之，乙醇暴露增强了HCV对先天免疫的抑制作用，这激活了病毒在肝脏中的传播，最终导致获得性免疫的损害。免疫反应的失调导致HCV感染细胞的清除受损、病毒持续存在、进行性肝损伤和慢性感染的建立，这是酒精中毒患者慢性丙型肝炎的结果。
Hepatitis C and alcohol are the most widespread causes of liver disease worldwide. Approximately 80% of patients with a history of hepatitis C and alcohol abuse develop chronic liver injury. Alcohol consumption in hepatitis C virus (HCV)-infected patients exacerbates liver disease leading to rapid progression of fibrosis, cirrhosis and even hepatocellular carcinoma. Hepatocytes are the main sites of HCV-infection and ethanol metabolism, both of which generate oxidative stress. Oxidative stress levels affect HCV replication and innate immunity, resulting in a greater susceptibility for HCV-infection and virus spread in the alcoholic patients. In this review paper, we analyze the effects of ethanol metabolism and other factors on HCV replication. In addition, we illustrate the mechanisms of how HCV hijacks innate immunity and how ethanol exposure regulates this process. We also clarify the effects of HCV and ethanol metabolism on interferon signaling—a crucial point for activation of anti-viral genes to protect cells from virus—and the role that HCV- and ethanol-induced impairments play in adaptive immunity which is necessary for recognition of virally-infected hepatocytes. In conclusion, ethanol exposure potentiates the suppressive effects of HCV on innate immunity, which activates viral spread in the liver and finally, leads to impairments in adaptive immunity. The dysregulation of immune response results in impaired elimination of HCV-infected cells, viral persistence, progressive liver damage and establishment of chronic infection that worsens the outcomes of chronic hepatitis C in alcoholic patients.