Hepatitis B and Delta Virus: Advances on Studies about Interactions between the Two Viruses and the Infected Hepatocyte

The mechanisms determining persistence of hepatitis B virus (HBV) infection and long-term pathogenesis of HBV-associated liver disease appear to be multifactorial. Although viral replication can be efficiently suppressed by the antiviral treatments currently available, viral clearance is generally not achieved since HBV has developed unique replication strategies, enabling persistence of its genome within the infected hepatocytes. Moreover, no direct antiviral therapy exists for the more than 15 million people worldwide that are also coinfected with the hepatitis delta virus (HDV), a defective virus that needs the HBV envelope proteins for propagation. The limited availability of robust HBV and HDV infection systems has hindered the understanding of the complex network of virus-virus and virus-host interactions that are established in the course of infection and slowed down progress in drug development. Since chronic HBV/HDV coinfection leads to the most severe form of chronic viral hepatitis, elucidation of the molecular mechanisms regulating virus-host interplay and pathogenesis are urgently needed. This article summarizes the current knowledge regarding the interactions among HBV, HDV, and the infected target cell and discusses the dependence of HDV on HBV activity and possible future therapeutic approaches.