PNAS：科学家发现新的艾滋病毒抑制蛋白

近日，科学家们已经确定了艾滋病病毒感染的人血液中新的艾滋病毒抑制蛋白。该蛋白叫CXCL4或PF-4，能结合艾滋病毒。这项研究是由Paolo Lusso医学博士领导。

CXCL4是一种趋化因子，帮助调节免疫细胞的运动。20世纪90年代中期，四个趋化因子中有三个是有Lusso, Robert Gall博士发现的。这些趋化因子以及CXCL4可调节感染者体内病毒的复制水平，从而影响HIV疾病进程。

据Lusso博士描述，CXCL4结合到艾滋病毒上的部位似乎与其它艾滋病毒的阻断抗体和药物的结合部位不同。研究团队确定了此结合位点在原子水平上的晶体结构，这可能有助于开发艾滋病毒治疗疫苗。

Lusso博士和他的同事们正在开展进一步研究，以便更好地了解CXCL4在HIV疾病中的作用。

doi:10.1073/pnas.1207314109
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Identification of the platelet-derived chemokine CXCL4/PF-4 as a broad-spectrum HIV-1 inhibitor

David J. Auerbach^a,¹, Yin Lin^a, Huiyi Miao^a, Raffaello Cimbro^a, Michelle J. DiFiore^a, Monica E. Gianolini^a,², Lucinda Furci^b, Priscilla Biswas^b, Anthony S. Fauci^a,³, and Paolo Lusso^a,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.