澳大利亚科学家完全清除小鼠类HIV感染

iavjssssmqee · 发表于 2011-2-12 12:43:41

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本帖最后由 iavjssssmqee 于 2011-2-12 12:47 编辑

HIV-like infection banished from mice

《新科学家》2011年2月4日报道
11:29 04 February 2011 by Wendy Zukerman

For the first time, an HIV-like infection has been cleared from an animal without the use of antiviral drugs. The infection was eliminated from mice using a human protein that peps up immune cells.

Marc Pellegrini from the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, and colleagues infected mice with lymphocytic choriomeningitis virus (LCMV), which causes a chronic infection that spreads throughout the body. "The virus overwhelms mice, mimicking the massive viral loads associated with HIV infection in humans," says Pellegrini.

Eight days after infection, some of the mice were injected with human interleukin-7 (IL-7) – a chemical messenger that plays a role in the development of immune cells – once a day for three weeks. The others received a placebo instead.

"Usually mice never clear this virus," says Pellegrini. But 30 days later, those given treatment had cleared most of the infection and removed all of it by 60 days.

Overactive response

The explanation seems to lie in a protein called SOCS3, which blocks the function of T-cells – a type of immune cell and therefore part of the body's system for fighting infection. At the beginning of an acute infection, SOCS3 becomes highly activated, suppressing the body's immune response. That sounds just the opposite of what you'd want. But it's a good thing because it stops T-cells being overzealous, which can cause damage to body tissue, says Pellegrini.

It becomes a problem when the body is trying to fight an overwhelming infection like HIV, he says: then the immune system puts on the brakes too early and the infection persists.

Blood tests taken throughout the experiment showed that IL-7 seemed to switch off the production of SOCS3, thereby ramping up the T-cell response.

Start and stop

This explanation was confirmed when the team knocked out the SOCS3 gene in a separate group of mice and infected them with LCMV. Immune cell numbers in these mice skyrocketed – T-cells increased sixfold compared with normal mice.

But knocking out SOCS3 showed the dangers of taking the immune brakes off. "Initially the mice mounted a robust immune response, but then it got out of hand," says Pellegrini. The mice developed mass inflammation and increased incidences of autoimmune diseases.

However, because IL-7 only affects T-cells, and not other types of immune cell, the researchers suggest that drugs could be developed that turn off SOCS3 for very short periods to reinvigorate T-cells without causing damage to the body.

Sharon Lewin at the Burnet Institute in Melbourne says the finding that IL-7 can clear the virus without the help of antiviral drugs is very interesting. Viruses like HIV use the host's cells to replicate, which makes it difficult to design antivirals that stop the virus without harming healthy cells.

"[Stopping a virus] without antivirals is something we haven't seen before," she says.

Journal reference: Cell, DOI: 10.1016/j.cell.2011.01.011

原英文报道：

http://www.newscientist.com/arti ... shed-from-mice.html

论文地址：
http://www.sciencedirect.com/sci ... lVersion=0&_use***10&md5=49ecc01cb3d8a6adc77a67309dc32ca9&searchtype=a

iavjssssmqee · 发表于 2011-2-12 12:45:51

完全清除小鼠类HIV感染

《新科学家》2011年2月4日报道

在不使用抗病毒药物的情形下，科学家首次使动物彻底摆脱了类HIV感染。完成这一病毒完全清除壮举的"英雄"是一种能够增强免疫细胞活性的人类蛋白。

来自澳大利亚墨尔本市沃尔特伊丽莎医学研究所（the Walter and Eliza Hall Institute of Medical Research）的Marc Pellegrini及其同事用淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染实验小鼠（该病毒可导致全身性慢性感染）。Pellegrini介绍说：“于是病毒击垮了小鼠，从而模拟出与人类HIV感染相似的极为可观的病毒载量。”

在感染后第八天，其中一些小鼠接受人类白细胞介素—7（IL-7，一种化学信使，在免疫细胞发育中扮演角色）注射，每天一次连续三周，其余小鼠则接受安慰剂注射。

Pellegrini指出：“在通常情形下，小鼠不可能完全清除这种病毒。” 但30天后，接受治疗的小鼠已清除了大部分感染，六十天后病毒被完全清除。

过度活跃的免疫响应

如何解释这个现象？看来SOCS3蛋白是其中关键。Pellegrini分析说，SOCS3阻止了T细胞的功能发挥，因而阻止了免疫系统部分功能发挥。急性感染刚开始时，SOCS3变得高度活跃，抑制了身体的免疫响应。这个过程听起来跟你的愿望背道而驰，但实际上却是好事一件，因为这一过程阻止了T细胞的过热行为（过热行为有损身体组织）。

但是，他同时指出：当身体尝试抵抗来势汹汹的HIV之类病毒感染时，这一过程就不敢令人恭维了，这是因为免疫系统过早地刹车，结果感染就会肆无忌惮地持续下去。

贯穿本实验始终的血液测试显示：IL-7看来关闭了SOCS3的生产过程，从而增强了T细胞的响应水平。

启动与停止

上述解释在研究小组将SOCS3基因从另外一组小鼠中敲除然后用LCMV进行感染时得到了证实。这些小鼠中的免疫细胞数量激增，其中T细胞与正常小鼠相比增加了六倍。

但是，敲除SOCS3又显示了取消免疫刹车的危险性。Pellegrini说：“开始时小鼠作出了强有力的免疫响应，但接下来就失控了。” 这些小鼠患上了广泛性感染并使自身免疫病的患病率提高了。

不过，因为IL-7只影响T细胞，对其它类型的免疫细胞并不产生影响，研究者因而建议：可以开发在一段极短时间内关闭SOCS3（以激励T细胞）而不会损伤组织的药物，

墨尔本贝尼特研究所（Burnet Institute）的Sharon Lewin说，有关IL-7能够在无需抗病毒药物帮助的情形下彻底清除该病毒（LCMV）的发现非常令人感兴趣。HIV之类的病毒利用宿主细胞进行复制，要想设计出不损害健康细胞的抗病毒药物难度就变得很大。

她说：“而无须抗病毒药物就能（阻止一种病毒），则是前所未见。”

参考文献： Cell, DOI: 10.1016/j.cell.2011.01.011

原英文报道：
http://www.newscientist.com/arti ... shed-from-mice.html

论文地址：
http://www.sciencedirect.com/sci ... lVersion=0&_use***10&md5=49ecc01cb3d8a6adc77a67309dc32ca9&searchtype=a

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