摘要
趋化因子受体是HIV进入靶细胞的必要协同受体,其识别是了解HIV病毒感染发病机制的重要突破。除了其通过结合协同受体阻断病毒进入的作用外,趋化因子在艾滋病发病机制中还有着其它功能。事实上,趋化因子可以抑制或增强艾滋病毒的复制从而影响病毒的生命周期。根据对艾滋病毒复制和传播的消极与积极不同影响,趋化因子对HIV 发病机制也有着不同的作用。CCL2 是一种特殊的趋化因子,其主要加强病毒复制和发病机制。无论是HIV感染本身还是暴露于病毒中都可诱导趋化因子及其受体CCR2的表达、并且能发现HIV感染者中CCL2/CCR2表达水平较高。CCL2/CCR2轴与高水平免疫激活和炎症紧密相关。即使对于正在接受抗逆转录病毒治疗的患者,炎症也是HIV 感染的标志之一。此外,CCL2对HIV复制的直接影响越来越明显。CCL2 /CCR2驱动效应的调节对HIV疾病过程有着重要影响。基于CCL2/CCR2轴的抑制作用,本文讨论了CCL2/CCR2和HIV以及新兴治疗方法之间复杂关系。
关键词: CCL2 CCR2艾滋病毒,炎症,发病机制,治疗。
图形摘要
Current Drug Targets
Title:The CCL2/CCR2 Axis in the Pathogenesis of HIV-1 Infection: A New Cellular Target for Therapy?
Volume: 17 Issue: 1
Author(s): Daniela Angela Covino, Michela Sabbatucci and Laura Fantuzzi
Affiliation:
关键词: CCL2 CCR2艾滋病毒,炎症,发病机制,治疗。
摘要: The identification of chemokine receptors as necessary co-receptors for HIV entry into target cells represented a breakthrough in the understanding of the pathogenesis of this viral infection. Since this initial discovery, it was unraveled that chemokines, in addition to their role in blocking viral entry by binding to co-receptors, have other functions in HIV pathogenesis. Indeed, chemokines can either inhibit or enhance HIV replication, and these effects may involve both entry and post-entry events of the viral life cycle. Depending on the balance of their negative versus positive effects on HIV replication and spreading, chemokines contribute to different outcomes of HIV pathogenesis. CCL2 is unique among the chemokines in that mostly enhancing effects on viral replication and pathogenesis have been reported. Either HIV infection itself or exposure to viral products can induce the expression of this chemokine and of its receptor CCR2, and high levels of CCL2/CCR2 are indeed found in HIV-infected subjects. The CCL2/CCR2 axis is tightly linked to the high level of immune activation and inflammation that is the hallmark of HIV infection even in patients undergoing antiretroviral therapy. In addition, more direct effects of CCL2 on HIV replication are becoming apparent. Thus, modulation of CCL2/CCR2-driven effects may have significant impact on HIV disease progression. In this review, we will discuss the complex interaction between CCL2/CCR2 and HIV and the emerging therapeutic approaches based on the inhibition of this axis.
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Cite this article as:
Daniela Angela Covino, Michela Sabbatucci and Laura Fantuzzi , The CCL2/CCR2 Axis in the Pathogenesis of HIV-1 Infection: A New Cellular Target for Therapy?, Current Drug Targets 2016; 17 (1) . https://dx.doi.org/10.2174/138945011701151217110917
DOI https://dx.doi.org/10.2174/138945011701151217110917 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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