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TRIM5-α蛋白：艾滋病治疗新靶点
2011-04-22 10:01 来源 爱爱医
2004年初，美国波士顿Dana Farber癌症研究所的研究人员发现了一种名为TRIM5-α的蛋白，这种蛋白可以有效遏制HIV病毒在体内的自我复制过程，这给艾滋病治疗带来了新的希望。本文主要介绍了TRIM5-α蛋白的发现过程、阻止HIV感染的作用机制及其治疗艾滋病的前景。
2004年2月，美国波士顿Dana Farber癌症研究所的研究人员在Nature杂志上发表文章，称他们在旧大陆猴体内发现一种名为TRIM5-α的蛋白能有效遏制HIV病毒体内的自我复制过程。这给艾滋病治疗带来了新的希望。
1 TRIM5-α蛋白发现过程
由于HIV病毒很难在实验室实验中传染给猴子细胞，科学家们普遍认为，动物细胞和人类细胞存在某种重大差异，导致动物细胞不受艾滋病病毒传染。
在将各种各样的动物，包括灵长类和非灵长类动物，暴露在HIV病毒下后，他们发现HIV不能影响旧大陆猴子（全世界的猴子可以大致分成两类：非洲和亚洲的旧大陆猴，以及中南美洲的新大陆猴）。特别是在几年前的研究中，研究人员发现即使让HIV病毒侵入旧大陆猴子的细胞，这些病毒也不能对那些细胞造成稳定的影响。
在经过了几年的研究后，科学家们在2004年2月Nature杂志上发表的文章称，在猴子细胞内保护其不受HIV感染的成分是TRIM5-α蛋白。
为了证明发现的能有效阻止HIV病毒的主要成分确实是TRIM5-α，科学家们采取了两个方法：首先，将恒河猴（一种旧大陆猴）的TRIM5-α蛋白成分注入通常易受HIV病毒感染的人类细胞中，之后那些细胞就变得对HIV病毒有抵抗力了；其次，将恒河猴细胞中的TRIM5-α成分减少或阻止它起作用，发现一旦TRIM5-α不再表现的话，那些恒河猴细胞就变得完全易受HIV病毒感染了。这些结果证明，TRIM5-α对于在恒河猴细胞阻止HIV病毒起着必要的和充分的作用。
经过对比恒河猴基因和人类基因后，发现恒河猴的一个称为TRIM5-α的基因与人类TRIM5-α基因所产生的蛋白质中有一个氨基酸不同，这一重要变化导致恒河猴TRIM5-α蛋白可以阻止艾滋病病毒复制。用猴源蛋白替代人类蛋白后发现，人类细胞也具有了抑制艾滋病病毒的能力。同时，研究还发现，只需转变人类蛋白质的一个氨基酸。就能降低细胞的易受感染性。
2 TRIM5-α蛋白阻止HIV感染的作用机制
研究发现，TRIM5-α蛋白阻止艾滋病病毒复制的机制可能是在HIV病毒侵入细胞前“裹住”HIV的保护壳，防止病毒脱去其保护性衣壳，来阻止它释放遗传物质，从而有效遏制HIV病毒在体内的自我复制过程。
研究还发现人类细胞中也有类似的TRIM5-α蛋白成分，但是比猴子细胞内的成分在阻止HIV病毒方面要逊色许多。TRIM5-α可能因为基因变异的缘故，在个体中的力量不太一样，这或许可以用以解释感染HIV病毒的人发病为何快慢有别。
3 TRIM5-α蛋白治疗艾滋病前景
这些关于TRIM5-α蛋白的研究为HIV感染的早期治疗和新疗法研究开辟了广阔的前景，一个可能的方法是通过基因疗法将猴TRIM5-α导入HIV感染者，以此挽救仍未被感染的细胞，但直接从猴子身上提取TRIM5-α作为药物不太现实的，因为量太少。科学家正在研究TRIM5-α的基因编码，对此做基因序列分析，然后用遗传工程方法把基因序列转到微生物或体外细胞上，以期能大量生产TRIM5-α蛋白。
另一个可能是利用这种蛋白质开发出新的艾滋病药物，增强人体内TRIM5-α蛋白的效能。这也需要先研究出TRIM5-α的基因编码，对此做基因序列分析，然后用遗传工程或其他的方法生产相关药物。
另外，还可以利用TRIM5-α蛋白来制备合适的HIV感染动物模型，并加快艾滋病疫苗的开发过程。
参考文献
英国研究表明，猕猴基因给艾滋病治疗带来希望
http://www.chinadaily.com.cn/gb/doc/2005-01/15/content_409292.htm
新发现的抗HIV-1蛋白质TRIM5α研究进展。军事医学科学院院刊
2005，29（3）287-290The cytoplasmic body component TRIM5 restricts HIV-1 infection in Old World monkeys.Nature，2004，427（6977）848-853
艾滋病不治会早死，早治才康复 艾滋病不治会早死，早治才康复 艾滋病不治会早死，早治才康复 艾滋病不治会早死，早治才康复
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| 图示∶2010年12月即将出版的《中国特色医疗金鉴》登载的刘君主任及其机构 |
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TRIM5-α protein: a new target for AIDS treatment
2011-04-22 10:01 Source Oi Hospital
In early 2004, Dana Farber Cancer Institute in Boston, researchers discovered a protein called TRIM5-α's, this protein can effectively curb HIV, self-replication process in the body, giving AIDS treatment brings new hope . This paper describes the discovery of TRIM5-α protein in the process, to prevent HIV infection and its mechanism prospects for treatment of AIDS.
February 2004, Dana Farber Cancer Institute in Boston, researchers published an article in the journal Nature, said they found in the Old World monkeys, a protein called TRIM5-α can effectively curb the HIV virus the body's self-replication process. This gives AIDS treatment has brought new hope.
1 TRIM5-α protein in the discovery process
HIV is difficult because the virus infection in laboratory experiments to monkey cells, scientists have generally agreed that animal cells and the existence of a significant difference in human cells, resulting in animal cells against HIV infection.
In the variety of animals, including primates and non-primate animals, exposure to HIV, the next, they found that HIV can not influence Old World monkeys (monkeys all over the world can be roughly divided into two categories: Africa and Asia Old World monkeys, as well as Central and South America's New World monkey). Especially in the study a few years ago, researchers found that even if the HIV virus to invade the Old World monkey cells, these viruses cause can not be stable on the impact of those cells.
After several years of study, scientists at the February 2004 article published in the journal Nature, said in monkey cells from HIV infection to protect its components TRIM5-α protein.
In order to prove that the virus can effectively prevent HIV is indeed the main component TRIM5-α, scientists have taken two approaches: first, the rhesus monkey (an Old World monkey) and TRIM5-α protein components into the often vulnerable to HIV virus-infected human cells, and then the cells become resistant to the virus of HIV; Second, cells in the rhesus monkey TRIM5-α ingredients work to reduce or stop it, once the TRIM5-α is no longer found in the words of the performance those monkey cells to become completely vulnerable to HIV viral infection. These results demonstrate that, TRIM5-α to prevent the HIV virus in rhesus monkey cells play a necessary and sufficient role.
Rhesus monkey and human genes by comparing gene and found that rhesus monkeys, a gene called TRIM5-α and human TRIM5-α gene protein produced by a different amino acid, which led to important changes in rhesus monkey TRIM5- α protein can block HIV replication. Alternative source of protein with a monkey human proteins found in human cells also have the ability to suppress HIV. Meanwhile, the study also found that only one amino acid change in human proteins. Can reduce the vulnerability of cells.
2 TRIM5-α protein in the mechanism to prevent HIV infection
Found, TRIM5-α protein in the mechanism to prevent replication of HIV may be HIV virus into cells in the former "wrapped" HIV's protective shell, stripped of its protection against the virus capsid, to prevent it from releasing genetic material, so as to effectively curb HIV virus in the body of self-replication process.
The study also found that human cells have a similar TRIM5-α protein composition, but the composition of a monkey cells in preventing HIV virus to with less. TRIM5-α gene variation may be due to the reason, the power of the individuals are not the same, which may be used to explain the incidence of people infected with HIV virus, why the speed is different.
3 TRIM5-α protein in the treatment of AIDS prospects
The TRIM5-α protein on the research and early treatment of HIV infection in studies of new therapies has opened up broad prospects for a possible approach is through gene therapy to the monkey TRIM5-α into HIV infection, in order to save not yet been infected cells, but extracted directly from the monkeys, TRIM5-α as a drug is not realistic, because the amount too small. Scientists are studying the gene encoding TRIM5-α, which do gene sequence analysis, and then use genetic engineering to microbial or in vitro gene to cells in order to mass production of TRIM5-α protein.
Another possibility is to use this protein to develop new AIDS drugs, enhanced TRIM5-α protein in the human body performance. This also need to work out the gene encoding TRIM5-α, which do gene sequence analysis, and then use the methods of genetic engineering or other production-related drugs.
In addition, TRIM5-α protein can be used to prepare a suitable animal model of HIV infection and to accelerate AIDS vaccine development process.
References
British studies have shown that monkeys gene therapy brings hope to AIDS
http://www.chinadaily.com.cn/gb/doc/2005-01/15/content_409292.htm
Newly discovered anti-HIV-1 protein TRIM5α Research. Bulletin of the Academy of Military Medical Sciences
2005,29 (3) 287-290The cytoplasmic body component TRIM5 restricts HIV-1 infection in Old World monkeys.Nature, 2004,427 (6977) 848-853
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