来自德国海德堡大学的科学家研究发现处于休眠状态的CD4+ T 细胞中,SAMHD1可以限制HIV-1的感染。

-2012年11月《自然-医学》

中文翻译


【题目】休眠的CD4+ T 细胞中SAMHD1限制HIV-1感染

【译文】与活化的CD4+ T细胞不同,休眠期CD4+ T细胞对HIV感染高度耐受。HIV-1进入后早期,一种主要的阻断限制了侵入病毒基因组的逆转录作用。本研究表明脱氧核苷三磷酸三磷酸水解酶SAMHD1阻止休眠期CD4+ T 细胞中HIV-1 RNA的反转录。 SAMHD1在外周血中循环和存在于淋巴样器官中的休眠CD4+ T细胞中高度表达。在未刺激的CD4+ T细胞中感染的早期限制通过病毒Vpx人工或自然地组装入HIV-1或HIV-2病毒中或添加外源性脱氧核苷,而被克服。通过携带Vpx的HIV,Vpx介导的SAMHD1蛋白酶体降解以及胞内脱氧核苷酸含量升高位于成功感染之前。伴随SAMHD1沉默的来自健康供者或来自具有Aicardi-Goutières综合症患者(SAMHD1无义突变)的休眠期CD4+ T使得HIV-1感染可能性变大。因此,在体内大量非循环CD4+ T细胞中,SAMHD1增强了对HIV-1感染的有效限制。旁路SAMHD1不足以病毒子代的释放,表明在HIV复制后期存在其他屏障。总之,这些发现可能揭示了干扰免疫逃逸和HIV-1 T细胞免疫病理学的新方法。

英文原稿


[Title]: SAMHD1 restricts HIV-1 infection in resting CD4+ T cells

[Authors]:Hanna-Mari Baldauf,1, 2, 14 Xiaoyu Pan,1, 14 Elina Erikson,1, 2 Sarah Schmidt,1 Waaqo Daddacha,3 Manja Burggraf,4 Kristina Schenkova,1 Ina Ambiel,1, 2 Guido Wabnitz,5 Thomas Gramberg,6 Sylvia Panitz,7 Egbert Flory,7 Nathaniel R Landau,8 Serkan Sertel,9 Frank Rutsch,10 Felix Lasitschka,11 Baek Kim,3, 12 Renate König,4, 13 Oliver T Fackler1 & Oliver T Keppler1, 2

[Abstract]Unlike activated CD4+ T cells, resting CD4+ T cells are highly resistant to productive HIV-1 infection. Early after HIV-1 entry, a major block limits reverse transcription of incoming viral genomes. Here we show that the deoxynucleoside triphosphate triphosphohydrolase SAMHD1 prevents reverse transcription of HIV-1 RNA in resting CD4+ T cells. SAMHD1 is abundantly expressed in resting CD4+ T cells circulating in peripheral blood and residing in lymphoid organs. The early restriction to infection in unstimulated CD4+ T cells is overcome by HIV-1 or HIV-2 virions into which viral Vpx is artificially or naturally packaged, respectively, or by addition of exogenous deoxynucleosides. Vpx-mediated proteasomal degradation of SAMHD1 and elevation of intracellular deoxynucleotide pools precede successful infection by Vpx-carrying HIV. Resting CD4+ T cells from healthy donors following SAMHD1 silencing or from a patient with Aicardi-Goutières syndrome homozygous for a nonsense mutation in SAMHD1 were permissive for HIV-1 infection. Thus, SAMHD1 imposes an effective restriction to HIV-1 infection in the large pool of noncycling CD4+ T cells in vivo. Bypassing SAMHD1 was insufficient for the release of viral progeny, implicating other barriers at later stages of HIV replication. Together, these findings may unveil new ways to interfere with the immune evasion and T cell immunopathology of pandemic HIV-1.    

原文地址

http://www.nature.com/nm/journal/v18/n11/abs/nm.2964.html

 

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