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趋化因子受体:它们在人类免疫缺陷病毒(HIV)致病性及对HIV感染的抗性中的作用

[Chemokine receptors: their role in human immunodeficiency virus (HIV) pathogenicity and resistance to HIV infections].

作者信息

Us Dürdal

机构信息

Hacettepe Universitesi Tip Fakültesi, Mikrobiyoloji ve Klinik Mikrobiyoloji Anabilim Dali, Ankara.

出版信息

Mikrobiyol Bul. 2003 Jan;37(1):75-87.

Abstract

Chemokines are the chemoattractant cytokines which function briefly in inflammatory processes and also act as regulatory bridge molecules between innate and acquired immunity. Chemokines mediate their effects by binding to cell surface receptors that belong to the seven transmembrane domain superfamily of proteins, which are found mainly on the surface of leucocytes, macrophages and lymphocytes. Besides the functions in the immune system, certain chemokine receptors also function as co-receptors, in addition to CD4 molecule, for human immunodeficiency virus (HIV) entry into the target cells. Of these a beta-chemokine receptor CCR5 and an alpha chemokine receptor CXCR4 are the major co-receptors required for macrophage-tropic and T cell-tropic viruses, respectively. Genetic analysis has revealed the importance of chemokine receptor genes in the disease progression, and the identification of genetic polymorphisms such as alterations in the CCR5 gene that prevent surface expression, leads explaining why some people with CCR5 mutation are protected from HIV infection. Today it is accepted that chemokine gene deletion mutations and high production of chemokines are the host factors which take place in the resistance mechanisms of HIV-infected non- or slow-progressors. Depending on these data, recent studies have focused on chemokine receptor inhibitors and/or chemokine antagonists as the new therapeutic strategies that prevent HIV from interacting with receptors and block HIV infection. In this review, latest developments in chemokine receptor researches with a particular focus on their roles in HIV pathogenesis and resistance to HIV infection, have been discussed.

摘要

趋化因子是一类趋化性细胞因子,在炎症过程中发挥短期作用,同时也作为天然免疫和获得性免疫之间的调节桥梁分子。趋化因子通过与属于七跨膜结构域蛋白质超家族的细胞表面受体结合来介导其作用,这些受体主要存在于白细胞、巨噬细胞和淋巴细胞表面。除了在免疫系统中的功能外,某些趋化因子受体除了CD4分子外,还作为人类免疫缺陷病毒(HIV)进入靶细胞的共受体发挥作用。其中,β趋化因子受体CCR5和α趋化因子受体CXCR4分别是嗜巨噬细胞病毒和嗜T细胞病毒所需的主要共受体。基因分析揭示了趋化因子受体基因在疾病进展中的重要性,鉴定出如CCR5基因改变导致表面表达缺失等基因多态性,这解释了为什么一些CCR5突变的人能够免受HIV感染。如今,人们普遍认为趋化因子基因缺失突变和趋化因子的高表达是HIV感染的非进展者或缓慢进展者抵抗机制中的宿主因素。基于这些数据,最近的研究集中在趋化因子受体抑制剂和/或趋化因子拮抗剂上,将其作为防止HIV与受体相互作用并阻断HIV感染的新治疗策略。在这篇综述中,讨论了趋化因子受体研究的最新进展,并特别关注了它们在HIV发病机制和对HIV感染的抵抗中的作用。

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