Preclinical development of TLR ligands as drugs for the treatment of chronic viral infections.

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.