Preclinical development of TLR ligands as drugs for the treatment of chronic viral infections
Preclinical development of TLR ligands as drugs for the treatment of chronic viral infections
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DOI：
10.1517/17460441.2012.689281
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发表时间：
2012-06
影响因子：
6.3
通讯作者：
Xiaoyong Zhang;Anke Kraft;R. Broering;J. Schlaak;U. Dittmer;Mengji Lu
中科院分区：
文献类型：
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作者：
Xiaoyong Zhang;Anke Kraft;R. Broering;J. Schlaak;U. Dittmer;Mengji Lu
Toll样受体（TLR）已被确定为病毒感染中先天性和适应性免疫应答的关键调节因子。最近的研究表明，TLR系统与慢性病毒感染中的病原体之间存在着显著的相互作用。因此，TLR配体在慢性病毒感染的治疗中具有巨大的潜力。涵盖的领域：本文综述了三种主要病毒感染的TLR配体的临床前检测方法：B型肝炎病毒（HBV），丙型肝炎病毒（HCV）和人类免疫缺陷病毒（HIV）。TLR配体在不同的细胞培养系统以及这些感染的动物模型中显示出有效的抗病毒活性，并诱导抗病毒细胞因子的产生，调节细胞免疫功能和体内抗病毒作用。鉴定意见：近年来的研究表明，在细胞培养系统和动物模型中，大量TLR配体的激活可以有效地对抗病毒感染。探索这些模型，进一步深入阐明TLR配体抗病毒活性的分子和免疫学机制对于将其开发成临床有用的药物是必要的。
Introduction: Toll-like receptors (TLRs) have been identified as key regulators of innate and adaptive immune responses in viral infection. Recent progress in this field revealed that there are significant interactions between the TLR system and pathogens in chronic viral infections. Therefore, TLR ligands have great potential for the treatment of chronic viral infections. Areas covered: This review provides an overview of the methodology for preclinical testing of TLR ligands for three major viral infections: hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). TLR ligands have shown potent antiviral activity in different cell culture systems as well as animal models for these infections and induce the production of antiviral cytokines, modulated cellular immunological functions and antiviral effects in vivo. Expert opinion: The recent progress in this field demonstrated that activation of a large number of TLR ligands is effective against viral infections in cell culture systems and animal models. Exploring these models, further in-depth elucidation of the molecular and immunological mechanisms of the antiviral activity of TLR ligands will be necessary to develop them into clinical useful drugs.