病毒编码的趋化因子和趋化因子受体在病毒感染中的作用。

Peter J Holst, Hans R Lüttichau, Thue W Schwartz, Mette M Rosenkilde
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引用次数: 17

摘要

大型DNA病毒,如痘病毒,特别是疱疹病毒,其逃避免疫系统并在普通人群中维持的能力是臭名昭著的。根据本研究中积累的知识,很明显,这些作用的重要机制是宿主编码的趋化因子和趋化因子受体的获取和修饰。所描述的病毒分子没有留下任何机会,并且彻底有效地破坏了宿主的免疫系统。通过这一过程,病毒通过抑制这些或有效的方式将有效的抗病毒反应转变为弱的th2驱动反应,从而确定了抗病毒反应中的关键分子。这里的例子是US28清除趋化因子,vMIP1-3吸引Th2细胞和调节细胞,MC148选择性地参与CCR8。UL33、UL78,特别是ORF74已经为病毒病理学和抗病毒治疗的可能靶点提供了重要的见解,而且很有可能会有更多的人跟进。在HHV8中,vMIP-2和趋化因子结合蛋白提供了有效的抗炎剂。这些药物的潜力已经在动物模型中得到了证明,并且可能以其天然或改良的形式在人类中代表有用的治疗方法。
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Virally encoded chemokines and chemokine receptors in the role of viral infections.

Large DNA viruses such as pox- and in particular herpesviruses are notorious in their ability to evade the immune system and to be maintained in the general population. Based on the accumulated knowledge reviewed in this study it is evident that important mechanisms of these actions are the acquisition and modification of host-encoded chemokines and chemokine receptors. The described viral molecules leave nothing to chance and have thoroughly and efficiently corrupted the host immune system. Through this process viruses have identified key molecules in antiviral responses by their inhibition of these or potent ways to alter an efficient antiviral response to a weak Th2-driven response. Examples here are the chemokine scavenging by US28, attractance of Th2 cells and regulatory cells by vMIP1-3 and the selective engaging of CCR8 by MC148. Important insights into viral pathology and possible targets for antiviral therapies have been provided by UL33, UL78 and in particular ORF74 and the chances are that many more will follow. In HHV8 vMIP-2 and the chemokine-binding proteins potent anti-inflammatory agents have been provided. These have already had their potential demonstrated in animal models and may in their native or modified forms represent useful therapies in humans.

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