乙肝病毒引发慢性乙肝患者的T细胞“自杀”

Hepatitis B virus triggers cell 'suicide' in patients with chronic infection

　

乙肝病毒会引发慢性感染患者的细胞“自杀”
2008年4月8日
来自伦敦大学学院(University College London)的科学家发现了乙肝康复者与慢性乙肝感染者的一个重要区别，乙型肝炎病毒(HBV)成功地引发慢性感染患者T细胞的“自杀”。这一发现为开发提高人体应对这种感染能力的疗法或疫苗提供了一个重要的新焦点。


研究人员分析了T细胞中的数千个基因，T细胞是控制HBV所需的免疫系统的关键角色。他们发现慢性感染患者的T细胞被触发“自杀”。这可能是决定这些患者的免疫系统为何不能对抗感染的一个重要因素，也是一个可能成为新疗法有用靶点的过程。他们的发现发表在今天的《临床研究杂志》上。


乙型肝炎病毒(HBV)是世界上最常见的病毒之一，是十大致命传染病之一。超过2.5亿人长期感染乙肝病毒，这可能导致肝硬化、肝功能衰竭或肝癌。在大多数受感染的成年人中，免疫系统能够很好地控制病毒，事实上，比目前任何可用的治疗方法都更有效。了解慢性感染患者的问题对开发新疗法至关重要。


首席作者，UCL感染与免疫分部的Mala Maini博士说:“我们使用微阵列基因芯片，从康复者和慢性感染的乙肝患者中筛选出5000多个T细胞基因。这导致了一项发现，后者的T细胞并没有成功地对病毒做出反应，而是被一种名为Bim的细胞本身的致死性蛋白触发自杀。我们现在正在研究推动这一结果的良好机制。

　

　

April 8, 2008
Scientists from UCL (University College London) have identified a key difference between people who can fight the Hepatitis B virus (HBV) off successfully and those who fail to do so – that a group of cells important in controlling the disease are triggered to ‘commit suicide’ in patients who are chronically infected. This discovery provides an important new focus for developing therapies or vaccines that boost the body’s ability to manage this infection.

The researchers analysed thousands of genes in T cells, critical players of the immune system required for control of HBV. They found that T cells from patients who were chronically infected were triggered to ‘commit suicide’. This could be an important factor in determining why these patients’ immune systems cannot fight the infection, and a process which could be a useful target for new treatments. Their findings are published today in the Journal of Clinical Investigation.

Hepatitis B virus (HBV) is one of the most common viruses in the world, and ranks as one of the top ten killer infectious diseases. More than 350 million people have long-term infection with HBV, which may lead to liver cirrhosis, liver failure or liver cancer. In the majority of adults infected, the immune system is able to control the virus very well and is, in fact, more effective than any currently available treatment. Understanding what goes wrong in people with chronic infection is crucial to the development of new therapies.

Lead author, Dr Mala Maini, UCL Division of Infection & Immunity, said: “We used microarray gene chips to screen more than 5,000 genes in T cells from both recovered and chronically infected Hepatitis B patients. This led to the discovery that, instead of successfully reacting to the virus, the T cells in the latter group were triggered to commit suicide by one of the cells’ own death-inducing proteins, called ‘Bim’. We are now looking into the fine mechanism driving this outcome.”

The paper’s first author, Ross Lopes, added: “If we can develop safe ways of blocking the suicidal tendency of the T cells, we may be able to prolong their survival, so they can do a better job of controlling Hepatitis B infection.”

The proportion of the world's population currently infected with HBV is estimated at between 3 and 6 per cent, but up to a third have been exposed. It is endemic in parts of Asia and Africa. Chronic Hepatitis B may eventually cause liver cirrhosis and liver cancer, a fatal disease with very poor response to current treatments. The infection is preventable by vaccination at a young age.

Source: University College London

https://www.sciencedaily.com/releases/2008/04/080408175224.htm