Animal models of chronic hepatitis delta virus infection host-virus immunologic interactions

Abstract

Hepatitis delta virus (HDV) is a defective RNA virus that has an absolute requirement for a virus belonging to the hepadnaviridae family like hepatitis B virus (HBV) for its replication and formation of new virions. HDV infection is usually associated with a worsening of HBV-induced liver pathogenesis, which leads to more frequent cirrhosis, increased risk of hepatocellular carcinoma (HCC), and fulminant hepatitis. Importantly, no selective therapies are available for HDV infection. The mainstay of treatment for HDV infection is pegylated interferon alpha; however, response rates to this therapy are poor. A better knowledge of HDV-host cell interaction will help with the identification of novel therapeutic targets, which are urgently needed. Animal models like hepadnavirus-infected chimpanzees or the eastern woodchuck have been of great value for the characterization of HDV chronic infection. Recently, more practical animal models in which to perform a deeper study of host virus interactions and to evaluate new therapeutic strategies have been developed. Therefore, the main focus of this review is to discuss the current knowledge about HDV host interactions obtained from cell culture and animal models.

Figure 1

Schematic representation of HDV virions describing all the components of the viral particle. l-HDAg: HDV Large antigen; S-HDAg: HDV short antigen; S-HBsAg: Small HBV surface antigen; M-HBsAg: Medium HBV surface antigen; l-HBsAg: Large HBV surface antigen; ssRNA: single-stranded RNA.

Figure 2

Schematic representation of the HDV viral cycle: (1) Binding to NTCP on human hepatocyte; (2) Uncoating; (3) Translocation of the ribonucleoprotein particle into the nucleus; (4) Transcription of the antigenome in the nucleolus.; (5) Production of genomic RNA in the nucleoplasm; (6) Transcription of the mRNA; (7) Translation of HDAg; (8) Ribonucleoparticle assembly; (9) Asotiation of HBsAg Virion production in the cytoplasm; (10) Virion release. HBV cccDNA: HBV covalently closed circular DNA. HBV mRNAs: HBV messenger RNAs.