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【资讯翻译】Counterattack of the hepatitis B virus

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发表于 2016-3-17 15:17:47 | 显示全部楼层 |阅读模式
Counterattack of the hepatitis B virus

The hepatitis B virus (HBV), which is up to 100 times more infectious than HIV, is primarily transmitted through blood or other bodily fluids. HBV infects liver cells and chronic infection can lead to serious health problems such as cirrhosis or liver cancer. According to the World Health organization, chronic hepatitis B affects nearly 240 million people worldwide, killing almost 800,000 people a year. Drugs are available to treat HBV, but they rarely cure the infection, and so the virus typically returns after the treatment ends.

In a study published in Nature this week, an international team led by researchers from the Faculty of Medicine at the University of Geneva (UNIGE), Switzerland, discovered how our cells defend themselves against HBV infection, but also how the virus fights back. This work represents an important advance in our understanding of HBV and suggests new avenues for the development of innovative therapeutic agents.

A protective host protein destroyed by the virus X protein

Our cells produce a large number of defence proteins to protect us from viruses. These so-called "restriction factors" are a first line of defence against viral infections, and constitute an important component of the innate immune response. However, little is known about how our cells defend themselves against HBV, and which restriction factors (if any) are involved.

After infecting liver cells, the circular HBV genome travels to the cell nucleus, where it is remains, as a circle, independent from the cell chromosomes. But what happens next? This is what Professor Michel Strubin, a microbiologist at the Faculty of Medicine at UNIGE, in collaboration with the University of Lyon (France) and Gilead Sciences, Inc. (Foster City, California, USA), discovered. Their work revealed that a host protein complex (Smc5/6) recognizes the HBV genome and then acts as a restriction factor to prevent the production of new viruses.

But the virus knows how to defend itself. "If the story ended there, the virus would no longer exist. It would be without counting on its remarkable adaptability" explains Michel Strubin. "The virus counterattacks by producing a small protein, called the X protein, whose function is destroy Smc5/6. It has the ability to bring this restriction factor to a part of the cell that acts as a trash can, and gets rid of it." With Smc5/6 gone, new viral particles can then be produced to infect neighbouring cells.

Inhibiting the virus X protein

This work raises the possibility of developing new therapeutic agents that target the X protein and prevent the virus escaping from liver cell defences. "Understanding this mechanism provides new therapeutic possibilities. Research continues to apply this fundamental discovery to the development of innovative drugs that could inhibit the X protein" highlights Dr. Simon Fletcher, from Gilead Sciences, Inc., whose team provided the in vivo verification of the discoveries made by the University of Geneva microbiologists.

Moreover, this mechanism could apply to other viruses. Indeed, the herpes viruses or the human papillomavirus—which can cause cervical cancer—have, just like HBV, circular genomes that are independent from the cell chromosomes. The researchers are now working to determine if Smc5/6 can target these viruses and, in turn, whether the viruses fight back. If so, preventing viral proteins from destroying Smc5/6 may be a useful strategy to prevent a variety of diseases which adversely affect the health of millions of people worldwide.

信源地址:http://medicalxpress.com/news/20 ... epatitis-virus.html

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发表于 2016-3-17 17:58:53 | 显示全部楼层
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发表于 2016-3-19 09:13:10 | 显示全部楼层
                     乙型肝炎病毒的反击

乙型肝炎病毒(HBV)感染比HIV高出100倍,主要通过血液或其他体液传播。HBV感染肝细胞后,慢性感染将导致一系列的健康问题比如肝硬化或肝癌。根据世界卫生组织(WHO)报道,慢性乙型肝炎影响了世界上将近2.4亿的人群,每年几乎有80万人死亡。抗病毒药物可用于治疗HBV,但是不能治愈,且终止治疗后容易复发。

本周,瑞士日内瓦大学(UNIGE)医学院在NATURE发表了一篇关于HBV感染的研究,阐明了机体抗HBV感染以及病毒反击的机制。这项研究增进了对HBV感染的认识,同时为药物的研发提供了新的治疗靶点。

病毒X蛋白

体内存在大量抗病毒感染蛋白,被称为“限制性因子”,是机体抗病毒感染的第一道防御系统,在固有免疫中起着重要作用。但是,关于这些“限制性因子”究竟怎样抗HBV感染,以及哪些蛋白参与其中仍然未知。

在HBV感染肝细胞以后,环状病毒基因组进入细胞核,并停留其中不受宿主细胞染色体的影响。但是接下来发生什么呢?日内瓦大学医学院的微生物学家Michel Strubin教授与法国里昂大学和美国Gilead公司合作发现,宿主蛋白复合物(Smc5/6)能够识别HBV基因,同时作为限制因子阻止病毒复制。

但是病毒仍然能够反击。Michel Strubin教授说“如果仅仅只有机体的防御功能,那么病毒将不复存在。但是病毒具有可变性。其能产生一种小分子蛋白即X蛋白,破坏宿主细胞的Smc5/6,并将其运输至溶酶体中使其降解。”当Smc5/6被破坏后,新的病毒将会产生并且感染邻近的细胞。

抑制病毒X蛋白

这项研究为HBV感染的治疗提供了新的靶点。通过以X蛋白为靶向,阻止病毒逃逸。“了解这种机制提供新的治疗可能性,在此基础上继续进行研究,希望可以发现能够抑制X蛋白的药物”Gilead公司的Simon Fletcher博士说。

而且,这种机制可能存在于其他的病毒感染过程中。比如疱疹病毒或者人乳头瘤病毒(能导致宫颈癌),都类似HBV,有环状基因而不受宿主染色体的影响。研究者正在探索是否Smc5/6对这类病毒也有效,以及病毒反击机制。如果Smc5/6的确具备抗病毒作用,那么阻止病毒对该蛋白的破坏将成为预防一系列世界流行性疾病的切入点。

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 楼主| 发表于 2016-3-21 08:50:30 | 显示全部楼层
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