PNAS:新发现一种HIV抑制蛋白——CXCL4

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据物理学家组织网5月29日报道，美国国家卫生研究院（NIH）的科学家在感染人类免疫缺陷病毒（HIV）病患的血液中，确认了新型的HIV抑制蛋白。在实验室的研究中，这种名为CXCL4或PF-4的蛋白质可与HIV直接结合，使其无法依附或进入人体细胞。相关研究报告发表在近日出版的美国《国家科学院院刊》（PNAS）上。

此项研究由NIH下属免疫调节实验室病毒发病机制部门的负责人保罗·卢索博士所主导。研究人员称，CXCL4隶属于名为趋化因子的分子家族，它能够帮助调节身体内部免疫细胞的运动。

20世纪90年代中期，科学家通过实验发现，4种趋化因子可发挥HIV抑制剂的功能。这些趋化因子连同CXCL4或能够调节病患体内的病毒复制水平，从而控制艾滋病的发展速度。

卢索表示，CXCL4在HIV“外套”上黏着的位置似乎与其他已知的、针对HIV的封闭抗体及药物的攻击位置不同。研究团队还力图与疫苗研究中心的科学家共同定义黏合部位原子水平的晶体结构，这有望在未来艾滋病的治疗和疫苗研制中发挥作用。

此外，CXCL4还在多个方面与其他4个主要的HIV抑制趋化因子不同：其他趋化因子需通过与一至两种细胞受体，即CCR5和CXCR4受体，相捆绑来抑制HIV感染，病毒可附着于这两种受体以进入免疫细胞，而CXCL4则可直接附着于病毒的外层表面之上；同时，CXCL4还能结合种类繁多的HIV菌株以阻止感染，而无需担心其对应的受体的特异性；最后，其他趋化因子主要由免疫细胞所制造，而CXCL4则由血小板所制成。

卢索及其同事还将开展进一步研究，以便更好地了解CXCL4在艾滋病中发挥的作用，并确定趋化因子在人体内是否也能如在实验中一样具有防护效应。

转自http://paper.sciencenet.cn/htmlpaper/201253113223462324720.shtm

楼主：ipsvirus

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Identification of the platelet-derived chemokine CXCL4/PF-4 as a broad-spectrum HIV-1 inhibitor

David J. Auerbacha,1, Yin Lina, Huiyi Miaoa, Raffaello Cimbroa, Michelle J. DiFiorea, Monica E. Gianolinia,2, Lucinda Furcib, Priscilla Biswasb, Anthony S. Faucia,3, and Paolo Lussoa,3

The natural history of HIV-1 infection is highly variable in different individuals, spanning from a rapidly progressive course to a long-term asymptomatic infection. A major determinant of the pace of disease progression is the in vivo level of HIV-1 replication, which is regulated by a complex network of cytokines and chemokines expressed by immune and inflammatory cells. The chemokine system is critically involved in the control of HIV-1 replication by virtue of the role played by specific chemokine receptors, most notably CCR5 and CXCR4, as cell-surface coreceptors for HIV-1 entry; hence, the chemokines that naturally bind such coreceptors act as endogenous inhibitors of HIV-1. Here, we show that the CXC chemokine CXCL4 (PF-4), the most abundant protein contained within the α-granules of platelets, is a broad-spectrum inhibitor of HIV-1 infection. Unlike other known HIV-suppressive chemokines, CXCL4 inhibits infection by the majority of primary HIV-1 isolates regardless of their coreceptor-usage phenotype or genetic subtype. Consistent with the lack of viral phenotype specificity, blockade of HIV-1 infection occurs at the level of virus attachment and entry via a unique mechanism that involves direct interaction of CXCL4 with the major viral envelope glycoprotein, gp120. The binding site for CXCL4 was mapped to a region of the gp120 outer domain proximal to the CD4-binding site. The identification of a platelet-derived chemokine as an endogenous antiviral factor may have relevance for the pathogenesis and treatment of HIV-1 infection

原文链接http://www.pnas.org/content/earl ... c-924e-324bde9a1f8e


发表于 2012-5-31 20:21 ipsvirus