title: Preclinical development of TLR ligands as drugs for the treatment of chronic viral infections.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Duisburg-Essen, Institute of Virology, University Hospital of Essen, Essen, Germany. xiaoyong.zhang@uni-due.de
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Zhang
authors.forename: Anke
authors.initials: A
authors.lastname: Kraft
authors.forename: Ruth
authors.initials: R
authors.lastname: Broering
authors.forename: Joerg F
authors.initials: JF
authors.lastname: Schlaak
authors.forename: Ulf
authors.initials: U
authors.lastname: Dittmer
authors.forename: Mengji
authors.initials: M
authors.lastname: Lu
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000277:Adjuvants, Pharmaceutic / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018929:Cell Culture Techniques; D002908:Chronic Disease; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004372:Ducks; D006678:HIV / Q000187:drug effects / Q000276:immunology; D016174:Hepacivirus / Q000187:drug effects / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007372:Interferons / Q000378:metabolism; D008024:Ligands; D008253:Macaca mulatta; D008392:Marmota; D051379:Mice; D002679:Pan troglodytes; D051193:Toll-Like Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014777:Virus Diseases / Q000188:drug therapy*
chemical_list: D000277:Adjuvants, Pharmaceutic; D000998:Antiviral Agents; D008024:Ligands; D051193:Toll-Like Receptors; D007372:Interferons