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Researchers for the first time reversed symptoms of HIV infection in a living animal using the technique of RNA interference. They constructed an antibody that targets T cells — in which HIV lurks — and linked it to a peptide carrying small RNA molecules, called siRNAs. The peptide helps these siRNAs enter T cells, where they silence certain host and virus genes crucial to the virus's replication.
Premlata Shankar, now at the Texas Tech University Health Sciences Center in El Paso, Sang-Kyung Lee of Hanyang University in Seoul, South Korea, and their colleagues injected the construct into mice genetically engineered to be easy to infect with HIV. The construct protected the mice from infection. It also restored the suppressed immune systems of mice that bore HIV-infected immune cells.

附录一 原文

Volume 134, Issue 4, 22 August 2008, Pages 577-586
  
T Cell-Specific siRNA Delivery Suppresses HIV-1 Infection in Humanized Mice

Priti Kumar, Hong-Seok Ban, Sang-Soo Kim, Haoquan Wu, Todd Pearson, Dale L. Greiner, Amale Laouar, Jiahong Yao, Viraga Haridas1, Katsuyoshi Habiro, Yong-Guang Yang, Ji-Hoon Jeong, Kuen-Yong Lee, Yong-Hee Kim, Sung Wan Kim, Matthias Peipp, Georg H. Fey, N. Manjunath, Leonard D. Shultz, Sang-Kyung Lee, and Premlata Shankar

Abstract
Summary
Human immunodeficiency virus type 1 (HIV-1) infection is a dynamic process involving high virus expression in lymphoid organs such as spleen and lymph nodes, rapid turnover of CD4 T cells and increased cell death in vivo (Pantaleo et al, 1993;Finkel et al, 1995;Ho et al, 1995). A number of pathophysiological mechanisms appear to contribute to the dramatic depletion of CD4 T lymphocytes in AIDS. Although viral load increases with disease progression, direct killing of CD4+ lymphocytes by HIV most probably cannot account for the magnitude of the loss of these cells during the course of HIV infection. Several years ago, it was suggested that CD4 T lymphocyte depletion may involve mechanisms whereby HIV infection primes a series of processes leading to programmed cell death (PCD) (Ameisen and Capron, 1991;Gougeon et al, 1991;Laurent-Crawford et al, 1991;Terai et al, 1991;Gougeon and Montagnier, 1993). Programmed cell death mediated by a process termed ‘apoptosis’ is the physiological cell death that occurs during embryogenesis, metamorphosis, normal tissue turnover and homeostasis. Apoptosis also plays a crucial role in negative growth control of the immune system. For example, thymocytes that have failed to rearrange their T cell receptor genes, or those that are autoreactive, are eliminated by apoptosis. The homeostatic control of peripheral lymphocytes is maintained by apoptosis which kills potentially autoreactive lymphocytes and limits the clonal expansion of lymphocytes during an immune response (Boise and Thompson, 1996). Exaggerated PCD can induce pathological situations and cause tissue destruction such as in fulminant hepatitis, in other diseases involving cytotoxic T lymphocyte (CTL)-induced tissue destruction, or in AIDS. The apoptotic pathways described below may account for depletion of CD4 T lymphocytes in AIDS patients. These pathways could be mediated either directly by virus replication as a consequence of viral gene expression, or indirectly through priming of uninfected cells to apoptosis when triggered by different agents. In addition to these pathways, a complementary cytopathic effect is probably provided by the immune system, since infected cells may be killed by HIV-specific CTLs or antibody-dependent cell-mediated cytotoxicity (ADCC). The relevance of apoptosis for AIDS pathogenesis is also discussed. 本人已认领该文编译,48小时后若未提交译文,请其他战友自由认领。 Researchers for the first time reversed symptoms of HIV infection in a living animal using the technique of RNA interference.
研究者利用RNA干扰技术首次缓解受HIV感染动物的症状。

They constructed an antibody that targets T cells — in which HIV lurks — and linked it to a peptide carrying small RNA molecules, called siRNAs.
他们设计了一个针对HIV感染T细胞的抗体,并且与一条携带有siRNA的肽链连接。

The peptide helps these siRNAs enter T cells, where they silence certain host and virus genes crucial to the virus's replication.
siRNA通过肽链的作用进入T细胞,然后封闭宿主和病毒对复制起重要作用的基因。

Premlata Shankar, now at the Texas Tech University Health Sciences Center in El Paso, Sang-Kyung Lee of Hanyang University in Seoul, South Korea, and their colleagues injected the construct into mice genetically engineered to be easy to infect with HIV.
得克萨斯理工大学卫生科学中心的Premlata Shankar和韩国汉阳大学的Sang-Kyung Lee及他们的同事,把产物注射入经基因工程改造的,HIV易感的小鼠体内。

The construct protected the mice from infection.
构造物可以保护小鼠免受感染。
It also restored the suppressed immune systems of mice that bore HIV-infected immune cells.

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作者:admin@医学,生命科学    2011-03-26 05:11
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