Kassela Katerina, Karakasiliotis Ioannis, Charpantidis Stefanos, Koskinas John, Mylopoulou Theodora, Mimidis Konstantinos, Sarrazin Christoph, Grammatikos Georgios, Mavromara Penelope
Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece.
Laboratory of Molecular Virology, Hellenic Pasteur Institute, Athens, Greece.
J Gen Virol. 2017 Jul;98(7):1713-1719. doi: 10.1099/jgv.0.000851. Epub 2017 Jul 15.
Hepatitis C virus (HCV) possesses a second open reading frame (ORF) within the core gene encoding an additional protein, known as the alternative reading frame protein (ARFP), F or core+1. The biological significance of the core+1/ARF protein remains elusive. However, several independent studies have shown the presence of core+1/ARFP antibodies in chronically HCV-infected patients. Furthermore, a higher prevalence of core+1/ARFP antibodies was detected in patients with HCV-associated hepatocellular carcinoma (HCC). Here, we investigated the incidence of core+1/ARFPantibodies in chronically HCV-infected patients at different stages of cirrhosis in comparison to chronically HCV-infected patients at earlier stages of disease. Using ELISA, we assessed the prevalence of anti-core+1 antibodies in 30 patients with advanced cirrhosis [model for end-stage liver disease (MELD) ≥15] in comparison with 50 patients with mild cirrhosis (MELD <15) and 164 chronic HCV patients without cirrhosis. 28.7 % of HCV patients with cirrhosis were positive for anti-core+1 antibodies, in contrast with 16.5 % of non-cirrhotic HCV patients. Moreover, there was significantly higher positivity for anti-core+1 antibodies in HCV patients with advanced cirrhosis (36.7 %) compared to those with early cirrhosis (24 %) (P<0.05). These findings, together with the high prevalence of anti-core+1 antibodies in HCV patients with HCC, suggest that core+1 protein may have a role in virus-associated pathogenesis, and provide evidence to suggest that the levels of anti-core+1 antibodies may serve as a marker for disease progression.
丙型肝炎病毒（HCV）在核心基因内拥有第二个开放阅读框（ORF），该阅读框编码一种额外的蛋白质，称为替代阅读框蛋白（ARFP），即F或core+1。core+1/ARF蛋白的生物学意义仍不清楚。然而，多项独立研究表明，慢性HCV感染患者体内存在core+1/ARFP抗体。此外，在HCV相关肝细胞癌（HCC）患者中检测到core+1/ARFP抗体的患病率更高。在此，我们调查了与疾病早期的慢性HCV感染患者相比，处于不同肝硬化阶段的慢性HCV感染患者中core+1/ARFP抗体的发生率。我们使用酶联免疫吸附测定（ELISA）评估了30例晚期肝硬化患者[终末期肝病模型（MELD）≥15]中抗core+1抗体的患病率，并与50例轻度肝硬化患者（MELD<15）和164例无肝硬化的慢性HCV患者进行了比较。28.7%的肝硬化HCV患者抗core+1抗体呈阳性，而非肝硬化HCV患者的这一比例为16.5%。此外，晚期肝硬化HCV患者中抗core+1抗体的阳性率（36.7%）显著高于早期肝硬化患者（24%）（P<0.05）。这些发现，连同HCV相关HCC患者中抗core+1抗体的高患病率，表明core+1蛋白可能在病毒相关发病机制中起作用，并提供证据表明抗core+1抗体水平可能作为疾病进展的标志物。
