摘要：维生素D补充剂被报道可以提高抗丙肝病毒治疗时实现持续病毒应答（SVR）的概率。我们的目标是确认体外潜在的维生素D在抑制HCV病毒生成的作用及探索这种抑制作用的机制。我们发现，维生素D3可以显著的抑制Huh7.5肝癌细胞中的HCV的合成。这些细胞表达CYP27B1，这个基因编码的酶是负责合成维生素D有激素活性的代谢物即骨化三醇。应用维生素D治疗导致骨化三醇的生成，并诱导骨化三醇的目标基因CYP24A1，表明这些细胞包含完整的维生素D新陈代谢和活动。值得注意的是，应用骨化三醇治疗可以抑制丙肝病毒。总的说来，这些发现说明维生素D是经由其活性代谢产物来发挥其抑制病毒的作用。这种抗病毒活性涉及干扰素的感应信号通路，导致β干扰素和干扰素刺激基因MxA的表达。HCV感染可通过抑制CYP24A1的感应来增加骨化三醇的合成，这个基因编码的酶负责骨化三醇分解的第一步。重要的是，维生素D、骨化三醇和α-干扰素协同抑制病毒的合成。结论：此研究第一次证明维生素D在体外传染性病毒合成体系中具有直接的抗病毒作用，提出了肝脏维生素D内分泌体系与丙肝病毒的一种相互影响，表明了维生素D作为天然抗病毒中介的角色。重要的是，我们的研究表明维生素D具有干扰素-节约效应，从而可以改善丙型肝炎患者抗病毒治疗效果。
吉林大学第一医院肝胆胰内科 姜翠 摘译
本文首次发表于[Hepatology. 2011;54(5):1570-1579]
Vitamin D: An innate antiviral agent suppressing hepatitis C virus in human hepatocytes
Abstract：Vitamin D supplementation was reported to improve the probability of achieving a sustained virological response when combined with antiviral treatment against hepatitis C virus (HCV). Our aim was to determine the in vitro potential of vitamin D to inhibit HCV infectious virus production and explore the mechanism(s) of inhibition. Here we show that vitamin D3 remarkably inhibits HCV production in Huh7.5 hepatoma cells. These cells express CYP27B1, the gene encoding for the enzyme responsible for the synthesis of the vitamin D hormonally active metabolite, calcitriol. Treatment with vitamin D3 resulted in calcitriol production and induction of calcitriol target gene CYP24A1, indicating that these cells contain the full machinery for vitamin D metabolism and activity. Notably, treatment with calcitriol resulted in HCV inhibition. Collectively, these findings suggest that vitamin D3 has an antiviral activity which is mediated by its active metabolite. This antiviral activity involves the induction of the interferon signaling pathway, resulting in expression of interferon-β and the interferon-stimulated gene, MxA. HCV infection increased calcitriol production by inhibiting CYP24A1 induction, the enzyme responsible for the first step in calcitriol catabolism. Importantly, the combination of vitamin D3 or calcitriol and interferon-α synergistically inhibited viral production. This study demonstrates for the first time a direct antiviral effect of vitamin D in an in vitro infectious virus production system. It proposes an interplay between the hepatic vitamin D endocrine system and HCV, suggesting that vitamin D has a role as a natural antiviral mediator. Importantly, our study implies that vitamin D might have an interferon-sparing effect, thus improving antiviral treatment of HCV-infected patients.
