转基因小鼠可能有助于对抗积极的肝炎形式

StephenW

Genetically Modified Mice May Help Fight Aggressive Form of Hepatitis
Publish Date: Monday, August 27, 2018

Efforts to develop an effective treatment for hepatitis D virus (HDV) have long been inhibited by laboratory mice not being susceptible to the virus. To address this, researchers were able to genetically humanize mice to be persistently infected with HDV, according to a study published in Science Translational Medicine.

"To our knowledge, this is the first time the entire HDV life cycle has been recapitulated in a mouse model with inheritable susceptibility to HDV," researcher Alexander Ploss, PhD, associate professor, Princeton University, said in a press release.

HDV is the most aggressive form of viral hepatitis, affecting 20 million people worldwide who are at high risk of developing liver fibrosis, cirrhosis, and liver cancer, according to the study. There is currently no cure for HDV, although an anti-hepatitis B virus (HBV) vaccine can prevent infection, the researchers noted.

Because HDV is only able to produce a single protein on its own, it requires additional proteins provided by HBV, according to the study. Patients who already have HBV can also contract HDV or be infected simultaneously by both viruses. However, the lack of antiviral treatments for HDV leaves these patients with limited options.

Although both viruses similarly infect the liver by binding to a surface protein called NTCP, the viruses are not able to recognize the protein in mice, which prevents infection and makes it difficult to study in the laboratory, according to the study.

To overcome this challenge, the researchers generated mice with the human NTCP protein in their liver cells, which subsequently allows infection by HBV and HDV. The results showed that HDV can establish persistent infection if the HBV proteins needed to propagate are provided.

The genetically modified mice allowed the researchers to evaluate the efficacy of 2 drugs in development for HDV infection. Although both drugs were able to suppress HDV levels, either in combination or individually, they did not completely cure the mice, as viral levels rebounded within weeks following treatment, according to the study.

"This is largely in line with recently reported data from clinical trials, showing the utility of our model for preclinical antiviral drug testing," study lead Benjamin Winer, graduate student, Princeton University, concluded in the press release.

StephenW

转基因小鼠可能有助于对抗积极的肝炎形式
发布日期：2018年8月27日，星期一

长期以来，开发有效治疗丁型肝炎病毒（HDV）的努力一直受到不易受病毒感染的实验室小鼠的抑制。根据发表在“科学转化医学”（Science Translational Medicine）上的一项研究，为了解决这个问题，研究人员能够对小鼠进行基因人源化以持续感染HDV。

普林斯顿大学副教授，研究员Alexander Ploss博士在一份新闻稿中说：“据我们所知，这是HDV生命周期第一次在具有遗传易感性HDV的小鼠模型中重演。”

据研究显示，HDV是最具攻击性的病毒性肝炎，影响全球2000万人患肝纤维化，肝硬化和肝癌的高风险。研究人员指出，尽管抗乙型肝炎病毒（HBV）疫苗可以预防感染，但目前还没有治愈HDV的方法。

该研究表明，由于HDV本身只能产生单一蛋白质，因此需要HBV提供的其他蛋白质。已经患有HBV的患者也可能感染HDV或被两种病毒同时感染。然而，缺乏针对HDV的抗病毒治疗使这些患者的选择有限。

虽然这两种病毒同样通过与称为NTCP的表面蛋白结合而感染肝脏，但这些病毒无法识别小鼠中的蛋白质，这可以预防感染并使其难以在实验室中进行研究。

为了克服这一挑战，研究人员在肝细胞中产生了人类NTCP蛋白的小鼠，随后允许HBV和HDV感染。结果表明，如果提供需要繁殖的HBV蛋白，HDV可以建立持续感染。

转基因小鼠允许研究人员评估2种药物在HDV感染发展中的功效。根据该研究，虽然这两种药物能够抑制HDV水平，无论是联合使用还是单独使用，都没有完全治愈小鼠，因为病毒水平在治疗后数周内反弹。

“这与最近报道的临床试验数据基本一致，显示了我们的模型用于临床前抗病毒药物测试的效用，”普林斯顿大学研究生Benjamin Winer在新闻发布会上得出结论。