C肝炎病毒感染導致60-80％的患者從急性到慢性，其肝臟演易變成脂肪變性，纖維化，肝硬化和肝細胞癌。在C肝炎病毒感染過程中，宿主與病毒之間的相互作用決定了大多數疾病進程。有一些研究指出病毒感染會引發細胞凋亡。伴隨C肝炎病毒感染急性期至慢性期的凋亡機制的變化尚不清楚。在我們先前的研究中，體外慢性C肝炎感染模仿臨床病人的病毒血症從急性階段（指數，平原，下降和沈默期）到慢性階段。在流式細胞分析中，於下降至沉默期間約有四分之一的急性感染細胞表現早期凋亡，但感染細胞在接下來的天數仍然存活下來。早期的凋亡細胞意指細胞的磷脂酰絲氨酸暴露在細胞膜外，但是它們仍然保持膜的完整性。然而，從急性至慢性感染，支持C肝炎感染細胞傾向於早期凋亡而非細胞死亡的機制仍不清楚。有些研究指出，c-Myc可以幫助細胞的增殖，在大多數癌症及某些病毒感染如腺病毒，人類免疫缺陷病毒或卡波西氏肉瘤疱疹病中。c-Myc主要調節麩醯胺酸,代謝以支持維持細胞增殖所需的TCA循環。因此，我們假設c-Myc通過調節麩醯胺酸,的代謝途徑來促進HCV感染細胞的增殖和克服早期細胞凋亡。首先，我們發現早期細胞凋亡率到達最高時，c-Myc表現增高於感染細胞。因此，我們檢測了處理c-Myc抑制劑和麩醯胺酸剝奪後的早期凋亡；結果顯示，c-Myc抑制劑處理後，早期凋亡被提升了。然而，在麩醯胺酸剝奪後早期凋亡率並無受到影響。此結果暗示早期凋亡增加並非依賴麩醯胺酸。此外，報導指出C肝炎病毒感染影響脂質平衡且最終促進脂肪肝，且已知脂質代謝對於C肝炎病毒感染是不可或缺的過程。脂質代謝可能是另一條調節病毒持續存的途徑且有助慢性C型肝炎感染。因此，我們還檢測麩醯胺酸,剝奪和c-Myc抑製劑處理後C型肝炎從急性至慢性階段脂質含量的變化。結果表明，谷氨酰胺剝奪導致脂質積累取決於不同的感染階段。總而言之，不同感染階段麩醯胺酸剝奪導致脂質的積累，且影響病毒蛋白的表現。因此，我們可以推測，c-Myc可能涉及調節早期凋亡，而麩醯胺酸,剝奪誘導脂質積累可能與病毒進入不同的感染階段相關。

Hepatitis C virus (HCV) causes 60-80% of patients whose livers easy to develop steatosis, fibrosis, cirrhosis, and hepatocellular carcinoma from acute to chronic infections. The interaction of host and virus determines the majority of disease progression during the HCV infection. Some studies indicated that the virus infection triggered cell apoptosis. The changes of apoptotic machinery accompanying HCV infection from acute to chronic stages are unclear. In our previous study, HCV chronic infection in vitro mimicked the clinical patient’s viremia at acute (exponential, plateau, declined and silencing phases) and chronic stages. In the FACS analysis, more than one-fourth of acute infected cells expressed early apoptosis in the declined to silencing phases, but infected cells further survived in the following days. Early apoptosis means that phosphatidylserine of cells is exposed on the external surface of the cell membrane, but they still retain membrane integrity. However, the mechanisms supporting HCV infected cells tending toward early apoptosis instead of cell death are unclear. Some research dictated that c-Myc could help cells to proliferate in most cancer and some virus infection such as Adenovirus, HIV or KSHV. c-Myc mainly coordinates the glutamine metabolism to support TCA cycle that is required for maintenance of cells proliferation. Hence, we hypothesis c-Myc-mediated metabolic pathway play a role in promoting proliferation of HCV infected cells and overcoming early apoptosis by regulation of glutamine. First, we found that c-Myc expression was elevated before the peak early apoptosis in infected cells. Hence, we examined the early apoptosis with c-Myc inhibitor treatment and glutamine-deprivation. The early apoptosis rate was elevated after c-Myc inhibitor treatment. However, the early apoptosis rates didn’t change when glutamine was removed from the medium. The data implied that the early apoptosis was glutamine-independent. Additionally, it has been reported that the HCV infection might affect the lipids homeostasis and finally promote the outcomes of the fatty liver disease. The lipids metabolism has been known as an indispensable process in HCV infection. Lipids metabolism might another pathway regulates viral persistence to help HCV chronic infection. Thus, we also detected the change of lipid contents from HCV acute to chronic stages after glutamine-deprivation and c-Myc inhibitor treatment. The result showed that the glutamine deprivation caused the lipids accumulation depending on the different infected stages. To conclude, the glutamine deprivation might induce the lipid accumulation and influence the viral proteins expression at different stages. Thus, we speculate that c-Myc might involve regulating the early apoptosis, whereas the glutamine deprivation inducing the lipids accumulation might affect the virus enter different infected stages. The mechanisms of c-Myc regulating early apoptosis in HCV infection need further elucidate.

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