據(jù)美國(guó)物理學(xué)家組織網(wǎng)6月29日?qǐng)?bào)道，美國(guó)科學(xué)家找到了細(xì)胞因子SAMHD1蛋白抑制骨髓細(xì)胞感染HIV（艾滋病病毒）的機(jī)制，新研究擴(kuò)展了人們對(duì)艾滋病患者免疫系統(tǒng)如何對(duì)付HIV以及HIV如何逃避免疫反應(yīng)的理解，從而找到阻止HIV感染或者阻止其在感染者體內(nèi)復(fù)制的新療法,。相關(guān)研究發(fā)表在6月30日出版的《自然》雜志上。
骨髓細(xì)胞是提供抗原的白血細(xì)胞的一個(gè)子集，對(duì)身體抵抗病毒和其他病原體的免疫反應(yīng)非常重要,。凱斯西儲(chǔ)大學(xué)醫(yī)學(xué)院艾滋病研究中心研究員杰克·斯科沃斯基的研究團(tuán)隊(duì)和美國(guó)斯托瓦斯醫(yī)學(xué)研究所的邁克爾·沃什本領(lǐng)導(dǎo)的團(tuán)隊(duì)合作發(fā)現(xiàn)，SAMHD1蛋白能感應(yīng)到諸如巨噬細(xì)胞和樹狀細(xì)胞等骨髓細(xì)胞感染到HIV-1病毒（HIV分為1型和2型,，1型是目前全球流行的主要毒株,，2型目前只在西非流行）和其他相關(guān)的免疫缺陷病毒，并阻止病毒副本在這些細(xì)胞內(nèi)的合成,，從而抑制HIV病毒感染,。
以前，科學(xué)家們一直認(rèn)為,，SAMHD1發(fā)生變異會(huì)引發(fā)一種名為AGS的癥狀,，這種癥狀和先天病毒感染一樣，要?dú)w咎于在病毒缺席時(shí),，免疫系統(tǒng)內(nèi)干擾素的不適當(dāng)誘導(dǎo),。因此,，SAMHD1和其他引發(fā)AGS的細(xì)胞蛋白能摒棄細(xì)胞的核酸碎片，預(yù)防這種干擾素系統(tǒng)被不適當(dāng)?shù)丶せ睢?/p>
現(xiàn)在,，斯科沃斯基團(tuán)隊(duì)發(fā)現(xiàn),，除了能預(yù)防不適當(dāng)?shù)淖陨砻庖叻磻?yīng)發(fā)生之外， SAMHD1也能通過有效干預(yù)病毒核酸的產(chǎn)生從而抑制骨髓細(xì)胞感染HIV,。
他們還發(fā)現(xiàn),，HIV-2和相關(guān)的免疫缺陷病毒（SIVsm/mac）能夠通過使用它們編碼的Vpx蛋白來干掉SAMHD1，從而越過骨髓細(xì)胞內(nèi)的保護(hù)機(jī)制,，使人感染病毒,。然而，令人感興趣的是,，與HIV-1相比,，諸如HIV-2等擁有Vpx的病毒更不容易引發(fā)疾病。斯科沃斯基表示,，這可能是因?yàn)橥ㄟ^能在骨髓細(xì)胞內(nèi)建立感染,，HIV-2等病毒激起了比HIV-1更強(qiáng)烈的免疫反應(yīng)。
斯科沃斯基表示,，操縱SAMHD1的功能可能會(huì)讓感染HIV-1患者對(duì)這種病毒產(chǎn)生更強(qiáng)烈的免疫反應(yīng),。科學(xué)家們下一步將研究SAMHD1用來抑制HIV-1感染的分子路徑,。（生物谷Bioon.com）
生物谷推薦原文出處：
Nature doi:10.1038/nature10195
Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein
Kasia Hrecka; Caili Hao; Magda Gierszewska; Selene K. Swanson; Malgorzata Kesik-Brodacka; Smita Srivastava; Laurence Florens; Michael P. Washburn; Jacek Skowronski
Macrophages and dendritic cells have key roles in viral infections, providing virus reservoirs that frequently resist antiviral therapies and linking innate virus detection to antiviral adaptive immune responses1, 2. Human immunodeficiency virus 1 (HIV-1) fails to transduce dendritic cells and has a reduced ability to transduce macrophages, due to an as yet uncharacterized mechanism that inhibits infection by interfering with efficient synthesis of viral complementary DNA3, 4. In contrast, HIV-2 and related simian immunodeficiency viruses (SIVsm/mac) transduce myeloid cells efficiently owing to their virion-associated Vpx accessory proteins, which counteract the restrictive mechanism5, 6. Here we show that the inhibition of HIV-1 infection in macrophages involves the cellular SAM domain HD domain-containing protein 1 (SAMHD1). Vpx relieves the inhibition of lentivirus infection in macrophages by loading SAMHD1 onto the CRL4DCAF1 E3 ubiquitin ligase, leading to highly efficient proteasome-dependent degradation of the protein. Mutations in SAMHD1 cause Aicardi–Goutières syndrome, a disease that produces a phenotype that mimics the effects of a congenital viral infection7, 8. Failure to dispose of endogenous nucleic acid debris in Aicardi–Goutières syndrome results in inappropriate triggering of innate immune responses via cytosolic nucleic acids sensors9, 10. Thus, our findings show that macrophages are defended from HIV-1 infection by a mechanism that prevents an unwanted interferon response triggered by self nucleic acids, and uncover an intricate relationship between innate immune mechanisms that control response to self and to retroviral pathogens.
