日前,，在《自然》雜志網(wǎng)站上的報(bào)告稱,，英國研究人員探明了人體內(nèi)一種蛋白質(zhì)對抗艾滋病病毒的原理，并有望在此基礎(chǔ)上開發(fā)出新的艾滋病治療方法,。
此前美,、法等國的研究人員曾發(fā)現(xiàn)，人體內(nèi)一種名為SAMHD1的蛋白質(zhì)能阻止艾滋病病毒在一些白細(xì)胞中的復(fù)制,，但對其中的原理并不清楚,。
英國曼徹斯特大學(xué)等機(jī)構(gòu)的研究人員發(fā)現(xiàn)，這種蛋白質(zhì)能降解脫氧核苷酸,，而脫氧核苷酸正是艾滋病病毒復(fù)制所需要的基礎(chǔ),。
領(lǐng)導(dǎo)研究的米歇爾·韋布說，艾滋病病毒的復(fù)制在艾滋病感染進(jìn)程中是關(guān)鍵的一步，如能阻止病毒復(fù)制,，就可有效遏制艾滋病的感染進(jìn)程,。研究人員未來可通過模擬相關(guān)生理過程，開發(fā)出新的艾滋病治療方法或艾滋病疫苗,。（生物谷 Bioon.com)
doi:10.1038/nature10623
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PMID:
HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase
David C. Goldstone, Valerie Ennis-Adeniran, Joseph J. Hedden, Harriet C. T. Groom, Gillian I. Rice, Evangelos Christodoulou, Philip A. Walker, Geoff Kelly, Lesley F. Haire, Melvyn W. Yap, Luiz Pedro S. de Carvalho, Jonathan P. Stoye, Yanick J. Crow, Ian A. Taylor & Michelle Webb
SAMHD1, an analogue of the murine interferon (IFN)-γ-induced gene Mg11 (ref. 1), has recently been identified as a human immunodeficiency virus-1 (HIV-1) restriction factor that blocks early-stage virus replication in dendritic and other myeloid cells2, 3 and is the target of the lentiviral protein Vpx, which can relieve HIV-1 restriction4, 5, 6, 7. SAMHD1 is also associated with Aicardi–Goutières syndrome (AGS), an inflammatory encephalopathy characterized by chronic cerebrospinal fluid lymphocytosis and elevated levels of the antiviral cytokine IFN-α8. The pathology associated with AGS resembles congenital viral infection, such as transplacentally acquired HIV. Here we show that human SAMHD1 is a potent dGTP-stimulated triphosphohydrolase that converts deoxynucleoside triphosphates to the constituent deoxynucleoside and inorganic triphosphate. The crystal structure of the catalytic core of SAMHD1 reveals that the protein is dimeric and indicates a molecular basis for dGTP stimulation of catalytic activity against dNTPs. We propose that SAMHD1, which is highly expressed in dendritic cells, restricts HIV-1 replication by hydrolysing the majority of cellular dNTPs, thus inhibiting reverse transcription and viral complementary DNA (cDNA) synthesis.
