丙型肝炎病毒（HCV）感染除直接损伤肝细胞导致病变外，还常诱导肝细胞脂质沉积，导致脂肪肝的发生。而脂肪肝易导致肝硬化，晚期发展为肝癌，最终危及生命。本课题组通过前期研究发现，HCV感染通过自噬降解载脂蛋白B（ApoB）。ApoB下降可导致脂质分泌下降，可能是HCV导致肝细胞脂质沉积的因素之一。为此，本研究拟拟通过HCV细胞感染模型，对HCV是否通过ER stress诱导的自噬降解宿主细胞ApoB，ApoB的降解是否导致宿主细胞脂质沉积以及脂质沉积对病毒复制的影响进行研究。另外，本课题还将对自噬降解ApoB的机制进行探索，确定ApoB的泛素化是否参与其被自噬降解。以期初步阐明HCV通过自噬降解ApoB诱导脂质沉积的机制。深入研究HCV诱导肝细胞脂肪沉积的机制，将拓展我们对慢性丙型肝炎致病机制的认识。

Except direct hepatocytes injuration, hepatitis C virus (HCV) infection can also induce lipid accumulation in hepatocytes, which leads to steatosis. Liver steatosis often leads to end-stage liver diseases with cirrhosis and hepatocellular carcinoma。Through prophase study, we found that HCV could degrade ApoB by autophagy. The degradation of ApoB is able to decrease lipid secretion, which may induce lipid accumulation. To determine whether HCV degrade ApoB by autophagy to induce lipid accumulation, we will use a HCV cellular infection model and determine if HCV infection can degrade ApoB through ER stress induced autophagy and if the degradation of ApoB would lead to lipid accumulation in host cells. We will also analyze the influence of lipid accumulation induced by ApoB-degradation on HCV replication. Beyond, if ubiquitinoylation of ApoB plays a role in the degradation by autophagy will be analyzed. This study may increase our knowledge about the pathological mechanism of chronic hepatitis C and may provide theoretical basis for prevention of liver steatosis in chronic hepatitis C.