美科学家发现HIV可感染造血干细胞 拓展艾滋病新疗法


美科学家发现HIV可感染造血干细胞 拓展艾滋病新疗法
2011-05-03 08:20:18 来源: 南方网
 
 

  (来源:《科学时报》)

  为拓展艾滋病新疗法提供了可能

美国科学家发现,HIV可隐藏在造血干细胞中。

  尽管当前的艾滋病病毒(HIV)/艾滋病(AIDS)治疗力争能够控制这种疾病,但任何治疗的最终目标都是完全消灭这种病毒。不幸的是,完全消灭HIV是一项非常艰巨的任务,因为这种病毒在休眠的CD4+ T细胞中建立了潜在的储藏库。美国科学家日前研究发现,HIV能够传染造血干细胞(HSC),因此,HIV的储藏库可能比之前的预想更为持久。研究人员认为,这一发现为拓展新的艾滋病疗法提供了可能。

  之前的研究表明,造血干细胞能够抵抗HIV的感染,然而已知的病毒储藏库却不能完全解释艾滋病的发病情况,这意味着还有其他潜伏性感染的储藏库。美国安阿伯市密歇根大学的Christoph C. Carter和同事在2010年发表的一项研究显示,HIV能够感染造血祖细胞(HPC),但所使用的试验却无法将造血干细胞与造血祖细胞中的其他细胞类型区分开来。

  如今,利用一种多向移植实验(也就是说,造血细胞被植入接受了尚不足以致命的辐射的小鼠体内,从而形成了多重血系,并持续了4到6周,这是对干细胞潜能的决定性测试),Carter等人发现,HIV确实能够感染造血干细胞。

  研究人员通过分析HIV用来侵入细胞的细胞受体是否影响了被感染的造血祖细胞,从而开始了目前的研究。HIV的包膜蛋白(Env)与CD4受体和趋化因子联合受体CXCR4或CCR5的相互作用使得HIV进入细胞。Carter等人在一个系统中形成了有缺陷的无毒HIV,在这里,他们能够变换Env蛋白的趋向性。此外,研究人员用GFP标记了HIV基因组,从而能够用流式细胞术隔离被感染的细胞。

  研究人员发现,包含有一个翻转CXCR4 Env蛋白的HIV微粒能够感染具有特定表型的细胞。相比之下,利用翻转CCR5 Env蛋白,病毒只能有效感染更多分化型细胞。接下来,研究人员利用群体集成试验发现,被翻转CXCR4 HIV感染的细胞能够形成源自未成熟造血祖细胞的群体,其中包括造血干细胞。相比之下,被翻转CCR5 HIV感染的细胞只形成很少的群体。

  为了证明翻转CXCR4 HIV能够感染造血干细胞,研究人员进行了多向移植试验,将被翻转CXCR4 HIV感染的人类造血祖细胞引入被辐射的小鼠体内。在移植20周后,在小鼠血液中检测到源自人类的淋巴和骨髓细胞。这意味着最初被HIV感染的细胞实际上是造血干细胞。

  研究人员在最近出版的《细胞—宿主与微生物》杂志上报告了这一研究成果。

  因此,治疗HIV的方法需要在缓慢分化的造血干细胞中消灭潜在的HIV储藏库。然而,研究人员指出,由于HIV的有效感染导致造血干细胞产生了细胞凋亡,因此与标准的抗逆转录病毒疗法相结合,造血干细胞疗法或许对于减少HIV储藏库是有效的。(编辑 张颖)

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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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U.S. scientists found that HIV infection of hematopoietic stem cells can develop new treatments for AIDS
2011-05-03 08:20:18 Source: WASHINGTON
(Source: "Science Times")

To develop the new therapy offers the possibility of AIDS

 

U.S. scientists have discovered, HIV can hide in hematopoietic stem cells.

Although the current HIV (HIV) / AIDS (AIDS) treatment and strive to control this disease, but the ultimate goal of any treatment is complete elimination of the virus. Unfortunately, the complete eradication of HIV is a very difficult task, because the virus in dormant CD4 T cells set up a potential repository. U.S. scientists have recently found, HIV can infect hematopoietic stem cells (HSC), therefore, HIV in the vault may be more durable than previously expected. The researchers believe that this discovery to develop new AIDS therapies possible.

Previous studies showed that hematopoietic stem cells resistant to HIV infection, the virus vault but it is known can not fully explain the incidence of AIDS, which means that there are other latent infection of the stores. University of Michigan, Ann Arbor, USA Christoph C. Carter and colleagues in 2010 published a study, HIV can infect hematopoietic progenitor cells (HPC), but the pilot was unable to use hematopoietic stem cells and hematopoietic progenitor cells distinguished from other cell types.

Today, transplantation experiments using a multi-directional (ie, hematopoietic cells were implanted received insufficient to deadly radiation in mice, thus forming a multiple blood lines, and continued for 4 to 6 weeks, which is potential of stem cells in the decisive test), Carter et al found that, HIV is indeed capable of infecting hematopoietic stem cells.

The researchers analyzed HIV receptors to invade cells is affected by the infection of hematopoietic progenitor cells, which started the current study. HIV envelope protein (Env) with CD4 and chemokine receptors CXCR4 or CCR5 co receptor interaction allows HIV to enter cells. Carter and others in a system of non-toxic form of defective HIV, where they can change the trend of the Env protein. In addition, the researchers tagged with GFP HIV genome, which can be isolated by flow cytometry of infected cells.

The researchers found that contains a flip CXCR4 Env protein of HIV particles can infect cells with a specific phenotype. In contrast, the use of flip CCR5 Env protein, the virus can effectively infect more differentiated cells. Next, the researchers found that using integration test groups, were turned CXCR4 HIV from infected cells can form groups of immature hematopoietic progenitor cells, including hematopoietic stem cells. In contrast, by turning CCR5 HIV-infected cells formed only small groups.

To prove flip CXCR4 HIV can infect hematopoietic stem cells, researchers conducted a number of tests to the transplant, will be overturned CXCR4 HIV infection of human hematopoietic progenitor cells into mice by radiation. After 20 weeks of transplantation, the blood was detected in mice from human lymphoid and bone marrow cells. This means that HIV infected cells initially are actually stem cells.

The researchers recently published in the "cell - host and microbes," the magazine reported the results of this study.

Therefore, the treatment approach needs to slow HIV differentiation of hematopoietic stem cells in the elimination of a potential HIV stores. However, the researchers pointed out that because HIV infection leads to the effective hematopoietic stem cells in apoptosis, and is therefore the standard combination antiretroviral therapy, hematopoietic stem cell therapy may be effective in reducing the HIV vault. (Editor Zhang Ying)

 
 
 
 
 

[ 作者:佚名    转贴自:本站原创    点击数:196    更新时间:2011-5-3    文章录入:nnb ]