Host-targeting agents for treatment of hepatitis B virus infection.
Hepatitis B virus (HBV) infection is a major cause of chronic liver disease, including liver cirrhosis, liver failure and hepatocellular carcinoma (HCC)-the second leading and fastest rising cause of cancer death world-wide. While de novo infection can be efficiently prevented by vaccination and chronic infection can be controlled using antivirals targeting the viral polymerase, the development of efficient antiviral strategies to eliminate the virus and thus to cure infection remains a key unmet medical need. The recent progress in the development of robust infectious HBV cell culture models now enables the investigation of the full viral life cycle, including a more detailed study of the molecular mechanisms of virus-host interactions responsible for viral persistence. The understanding of these virus-host interactions will be instrumental for the development of curative treatments. Host-dependency factors have recently emerged as promising candidates to treat and prevent infection by various pathogens. This review focuses on the potential of host-targeting agents (HTAs) as novel antivirals to treat and cure HBV infection. These include HTAs that inhibit de novo and re-infection, synthesis and spread of cccDNA as well as development of immune-based approaches eliminating or curing infected hepatocytes, including the eradication of viral cccDNA.
Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France; Université de Strasbourg, 67000 Strasbourg, France; Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Nouvel Hôpital Civil, 67000 Strasbourg, France; Liver Center and Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, United States. Electronic address: thomas.baumert@unistra.fr.
Thomas F
TF
Baumert
Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France; Université de Strasbourg, 67000 Strasbourg, France.
Eloi R
ER
Verrier
Department of Internal Medicine 2/Molecular Biology, University Hospital Freiburg, D-79106 Freiburg, Germany.
Michael
M
Nassal
Liver Center and Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, United States.
Raymond T
RT
Chung
Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France; Université de Strasbourg, 67000 Strasbourg, France.
Mirjam B
MB
Zeisel
D000998:Antiviral Agents / Q000302:isolation & purification* / Q000494:pharmacology*; D006509:Hepatitis B / Q000473:pathology*; D054884:Host-Pathogen Interactions / Q000187:drug effects*; D006801:Humans
D000998:Antiviral Agents