Abstract：
Chronic hepatitis C virus infection (HCV) causes liver inflammation and fibrosis, leading to the development of severe liver disease, such as cirrhosis or hepatocellular carcinoma (HCC). Approval of direct-acting antiviral drug combinations has revolutionized chronic HCV therapy, with virus eradication in >98% of the treated patients. The efficacy of these treatments is such that it is formally possible for cured patients to carry formerly infected cells that display irreversible transcriptional alterations directly caused by chronic HCV Infection. Combining differential transcriptomes from two different persistent infection models, we observed a major reversion of infection-related transcripts after complete infection elimination. However, a small number of transcripts were abnormally expressed in formerly infected cells. Comparison of the results obtained in proliferating and growth-arrested cell culture models suggest that permanent transcriptional alterations may be established by several mechanisms. Interestingly, some of these alterations were also observed in the liver biopsies of virologically cured patients. Overall, our data suggest a direct and permanent impact of persistent HCV infection on the host cell transcriptome even after virus elimination, possibly contributing to the development of HCC.
摘要：
慢性丙型肝炎病毒感染（HCV）引起肝脏炎症和纤维化，导致严重肝脏疾病的发展，如肝硬化或肝细胞癌（HCC）。直接作用抗病毒药物组合的批准彻底改变了慢性HCV治疗，在>98%的治疗患者中根除病毒。这些治疗的功效使得治愈的患者正式可能携带显示由慢性HCV感染直接引起的不可逆转录改变的先前感染的细胞。结合两种不同持续感染模型的差异转录组，我们观察到在完全消除感染后,感染相关转录本出现重大逆转.然而,少量转录本在先前感染的细胞中异常表达。在增殖和生长停滞的细胞培养模型中获得的结果的比较表明，永久性转录改变可以通过几种机制建立。有趣的是,在病毒学治愈患者的肝活检中也观察到其中一些改变.总的来说,我们的数据表明，即使在病毒消除后，持续的HCV感染对宿主细胞转录组的直接和永久的影响，可能有助于HCC的发展。
