New York City rats provide a gift to virologists Despite the development of curative drugs for hepatitis C virus (HCV) infection, global eradication of HCV will likely require a prophylactic vaccine. Progress toward a vaccine has been impeded by the absence of mouse models suitable for studying the immune response to HCV. Billerbeck et al. found that a HCV-related virus isolated from New York City rats produces an infection in laboratory mice that shares several immunological features with human infections (see the Perspective by Klenerman and Barnes). Their initial analyses of the infected mice revealed that acute clearance of the virus was dependent on T cells but not on natural killer cells. Science, this issue p. 204; see also p. 129 A mouse model may provide mechanistic insights into the immune response to hepatitis C virus infection. An estimated 71 million people worldwide are infected with hepatitis C virus (HCV). The lack of small-animal models has impeded studies of antiviral immune mechanisms. Here we show that an HCV-related hepacivirus discovered in Norway rats can establish high-titer hepatotropic infections in laboratory mice with immunological features resembling those seen in human viral hepatitis. Whereas immune-compromised mice developed persistent infection, immune-competent mice cleared the virus within 3 to 5 weeks. Acute clearance was T cell dependent and associated with liver injury. Transient depletion of CD4+ T cells before infection resulted in chronic infection, characterized by high levels of intrahepatic regulatory T cells and expression of inhibitory molecules on intrahepatic CD8+ T cells. Natural killer cells controlled early infection but were not essential for viral clearance. This model may provide mechanistic insights into hepatic antiviral immunity, a prerequisite for the development of HCV vaccines.

中文翻译：

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急性和慢性肝炎病毒感染的小鼠模型

纽约市老鼠为病毒学家提供了一份礼物 尽管已经开发出治疗丙型肝炎病毒 (HCV) 感染的治疗药物，但全球根除 HCV 可能需要预防性疫苗。由于缺乏适合研究 HCV 免疫反应的小鼠模型，疫苗的进展受到阻碍。比勒贝克等人。发现从纽约市大鼠中分离出的 HCV 相关病毒会在实验室小鼠中产生感染，该感染与人类感染具有多种免疫学特征（参见 Klenerman 和 Barnes 的观点）。他们对受感染小鼠的初步分析表明，病毒的急性清除依赖于 T 细胞，而不是自然杀伤细胞。科学，这个问题 p。204; 另见第。129 小鼠模型可以提供对丙型肝炎病毒感染的免疫反应的机制见解。全世界估计有 7100 万人感染了丙型肝炎病毒 (HCV)。小动物模型的缺乏阻碍了抗病毒免疫机制的研究。在这里，我们表明在挪威大鼠中发现的一种 HCV 相关的肝病毒可以在实验室小鼠中建立高滴度的嗜肝感染，其免疫学特征类似于人类病毒性肝炎中所见的免疫学特征。免疫受损的小鼠会出现持续感染，而免疫功能正常的小鼠会在 3 到 5 周内清除病毒。急性清除率依赖于 T 细胞并与肝损伤相关。感染前 CD4+ T 细胞的短暂消耗导致慢性感染，其特征是肝内调节性 T 细胞水平高，肝内 CD8+ T 细胞表达抑制分子。自然杀伤细胞控制早期感染，但不是清除病毒所必需的。该模型可以提供对肝脏抗病毒免疫的机制见解，这是开发 HCV 疫苗的先决条件。