Background Hepatitis C virus (HCV) and hepatitis B virus (HBV) cause chronic hepatitis with important clinical differences. HCV causes hepatic steatosis and insulin resistance, while HBV confers increased risk of liver cancer. We hypothesised these differences may be due to virus-specific effects on mitochondrial function. Methods Seahorse technology was utilised to investigate effects of virus infection on mitochondrial function. Cell based assays were used to measure mitochondrial membrane potential and quantify pyruvate and lactate. Mass spectrometry was performed on mitochondria isolated from HBV expressing, HCV infected and control cells cultured with isotope-labelled amino acids, to identify proteins with different abundance. Altered expression of key mitochondrial proteins was confirmed by real time PCR and western blot. Results Reduced mitochondrial function and ATP production were observed with HCV infection and HBV expression. HCV impairs glycolysis and reduces expression of genes regulating fatty acid oxidation, promoting lipid accumulation. HBV causes lactate accumulation by increasing expression of lactate dehydrogenase A, which converts pyruvate to lactate. In HBV expressing cells there was marked enrichment of pyruvate dehydrogenase kinase, inhibiting conversion of pyruvate to acetyl-CoA and thereby reducing its availability for mitochondrial oxidative phosphorylation. Conclusions HCV and HBV impair mitochondrial function and reduce ATP production. HCV reduces acetyl-CoA availability for energy production by impairing fatty acid oxidation, causing lipid accumulation and hepatic steatosis. HBV has no effect on fatty oxidation but reduces acetyl-CoA availability by disrupting pyruvate metabolism. This promotes lactic acidosis and oxidative stress, increasing the risk of disease progression and liver cancer.

中文翻译：

---

乙型肝炎病毒和丙型肝炎病毒通过不同的代谢途径影响线粒体功能，解释了慢性肝炎的病毒特异性临床特征

背景 丙型肝炎病毒（HCV）和乙型肝炎病毒（HBV）引起慢性肝炎，具有重要的临床差异。 HCV 会导致肝脂肪变性和胰岛素抵抗，而 HBV 会增加患肝癌的风险。我们假设这些差异可能是由于病毒对线粒体功能的特异性影响所致。方法利用Seahorse技术研究病毒感染对线粒体功能的影响。基于细胞的测定用于测量线粒体膜电位并定量丙酮酸盐和乳酸。对从用同位素标记的氨基酸培养的 HBV 表达细胞、HCV 感染细胞和对照细胞中分离的线粒体进行质谱分析，以鉴定不同丰度的蛋白质。通过实时 PCR 和蛋白质印迹证实了关键线粒体蛋白表达的改变。结果 HCV 感染和 HBV 表达导致线粒体功能和 ATP 产生减少。 HCV 损害糖酵解并减少调节脂肪酸氧化的基因表达，促进脂质积累。 HBV 通过增加乳酸脱氢酶 A 的表达来引起乳酸积累，该酶将丙酮酸转化为乳酸。在 HBV 表达细胞中，丙酮酸脱氢酶激酶显着富集，抑制丙酮酸转化为乙酰辅酶A，从而降低其线粒体氧化磷酸化的可用性。结论 HCV 和 HBV 损害线粒体功能并减少 ATP 产生。 HCV 通过损害脂肪酸氧化来降低乙酰辅酶A用于能量产生的可用性，导致脂质积累和肝脂肪变性。 HBV 对脂肪氧化没有影响，但会通过破坏丙酮酸代谢来降低乙酰辅酶 A 的可用性。这会促进乳酸酸中毒和氧化应激，增加疾病进展和肝癌的风险。