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| 治愈慢乙肝：USC新乙肝治疗方案或仅需一个月
慢性乙肝病毒感染，目前仍是一个终身性的疾病且没有有效的治愈手段，然而据一项最新的南加利福尼亚大学（USC）研究结果显示，通过一系列的攻击乙肝病毒将来有望彻底的被从人体内清除。
多数健康成年人感染乙肝病毒后将会产生保护性免疫能力，感染后只需几个月便可治愈或自愈。但如果是由母婴传播导致的儿童HBV感染却是几乎不可能彻底的将体内的乙肝病毒清除。相反的，这些感染的儿童多数将会发展为终身携带乙肝病毒而成为乙肝病毒携带者或进展为其他疾病。
据美国疾病控制与预防中心2013年的数据显示，在美国约有110万人感染乙肝病毒，USC致力于攻克如今的“邪恶问题”，其中就包括感染性疾病。
“肝巨噬细胞”——肝脏的免疫细胞，其能清除外来物质和毒物，就像一个垃圾处理系统似的，这一细胞有望成为未来治疗的靶标， 南加州大学Keck医学院分子微生物学和免疫学教授 Jing-hsiung James Ou 说道。
“孕妇病毒抗原可以教后代的肝巨噬细胞对被称为CTLs的步兵白血细胞（foot soldier white blood cells ）形成自我压制，”该研究主要研究人员 Ou 在发表在5月3日 Immunity 杂志上的研究上说道。“因此，一旦婴儿暴露于这些病毒当中，婴儿的‘垃圾处理系统’将会抑制他自己的免疫系统去攻击病毒。我们可以在老鼠模型中消耗巨噬细胞，激活CTLs并清除乙肝病毒。”
该研究给治愈乙肝病毒感染提供了一条新的途径，Ou 说。他的研究团队揭露了HBV e 抗原的功能，以前这仍是一个谜，Ou 补充道。
在老鼠模型中，实验组来自感染乙肝病毒的雌鼠，而对照组则来自没有感染乙肝病毒的雌鼠。研究人员将HBV诱导DNA引进子代老鼠的肝脏中从而产生HBV。
经过28周的试验观察发现，实验组的肝巨噬细胞展开对其步兵CTLs进行攻击。换句话说，HBV阳性雌鼠分娩的子鼠白细胞由于细胞队伍里面出现叛徒而较弱。
为了从免疫系统中移出巨噬细胞从而使感染的HBV免遭清除，Ou 和他的同事向测试组注射了杀害这些叛徒的药物。研究人员在HBV DNA被引进去之前每两天来回重复该步骤，并在HBV DNA 被引进后每五天重复一次。研究人员总共注射了四次药物。
该药物去除巨噬细胞并恢复了正常CTL白细胞的活性，从而在四周后清除了乙肝病毒，OU 说，他将会在动物身上对该试验进行更深入的研究，从而确保在开始临床试验前该药物的安全性。
“这则研究开启了一扇门，”他说道。“未来，慢性HBV感染的治疗或许仅需一个月而不是终身治疗。”
英文原文
Maternal-Derived Hepatitis B Virus e Antigen Alters Macrophage Function in Offspring to Drive Viral Persistence after Vertical Transmission
Chronic hepatitis B infection, a lifetime disease with no effective cure, could one day be cleared from a person's system with a series of shots, according to a new USC study.
Most healthy adults infected with HBV will develop protective immunity, healing their own bodies within a few months. But children who acquired the virus from their mothers are unable to scrub HBV from their systems. Instead these individuals are fated to live with the virus for the rest of their lives.
About 1.1 million people in the United States have chronic HBV infection, reported the Centers for Disease Control and Prevention in 2013. USC is devoted to attacking today's "wicked problems," which include infectious diseases.
"Hepatic macrophages"—liver immune cells that eliminate foreign substances and toxins like a garbage disposal system—could be the target of future treatment, said Jing-hsiung James Ou, a professor of molecular microbiology and immunology at the Keck School of Medicine of USC.
"Maternal viral antigens teach the offspring's hepatic macrophages to suppress foot soldier white blood cells called CTLs," said Ou, senior author of the article published May 3 in Immunity, a Cell journal. "Therefore, when babies are exposed to the virus, the baby's 'garbage disposal units' will suppress its own immune system from fighting off the infection. We were able to deplete macrophages in a mouse model, activate CTLs and clear the virus."
The study paves a path to curing chronic HBV infection, Ou said. His research unveils the function of HBV e antigen, which was previously a mystery, Ou added.
In a mouse model, the experimental group came from mothers with HBV, whereas the control group came from mothers without HBV. Scientists introduced HBV-inducing DNA into offspring mouse liver to produce HBV.
Measurements taken throughout the 28-week experiment found that the test group's hepatic macrophages turned against their foot soldier CTLs. In other words, white blood cells in the offspring of HBV-positive mice were weakened because of renegades within the ranks.
To remove macrophages that prevented the immune system from eliminating HBV infection, Ou and his colleagues injected the test group with a drug that slays these traitors. Researchers performed the procedure two days before and once every five days after HBV DNA was administered. In total, researchers dispensed the drugs four times.
The drug removed macrophages and restored normal CTL white blood cell activity, leading to HBV clearance after about four weeks. Ou said he will further his research in animal studies, which is essential to ensure the safety of the drug before the initiation of clinical trials.
"This study opens doors," he said. "In the future, clinical treatment for chronic HBV infection may last merely one month rather than a lifetime.
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发表于 2016-5-4 16:16
