University of Duisburg-Essen, Institute of Virology, University Hospital of Essen, Essen, Germany.
Expert Opin Drug Discov. 2012 Jul;7(7):597-611. doi: 10.1517/17460441.2012.689281. Epub 2012 May 19.
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.
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.
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.
Toll 样受体 (TLRs) 已被确定为病毒感染中固有和适应性免疫反应的关键调节剂。该领域的最新进展表明，TLR 系统与慢性病毒感染中的病原体之间存在显著相互作用。因此，TLR 配体在慢性病毒感染的治疗中有很大的潜力。
本文综述了 TLR 配体在三种主要病毒感染（乙型肝炎病毒 (HBV)、丙型肝炎病毒 (HCV) 和人类免疫缺陷病毒 (HIV)) 的临床前测试方法。TLR 配体在不同的细胞培养系统和这些感染的动物模型中表现出强大的抗病毒活性，并诱导抗病毒细胞因子的产生、调节细胞免疫功能和体内的抗病毒作用。
该领域的最新进展表明，大量 TLR 配体的激活在细胞培养系统和动物模型中对病毒感染有效。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，将有助于将其开发成临床有用的药物。
