Abstract
The human Hepatitis Delta Virus (HDV) is unique among all viral pathogens. Encoding only one protein (Hepatitis Delta Antigen; HDAg) within its viroid-like self-complementary RNA, HDV constitutes the smallest known virus in the animal kingdom. To disseminate in its host, HDV depends on a helper virus, the human Hepatitis B virus (HBV), which provides the envelope proteins required for HDV assembly. HDV affects an estimated 15–20 million out of the 240 million chronic HBV-carriers and disperses unequally in disparate geographical regions of the world. The disease it causes (chronic Hepatitis D) presents as the most severe form of viral hepatitis, leading to accelerated progression of liver dysfunction including cirrhosis and hepatocellular carcinoma and a high mortality rate. The lack of approved drugs interfering with specific steps of HDV replication poses a high burden for gaining insights into the molecular biology of the virus and, consequently, the development of specific novel medications that resiliently control HDV replication or, in the best case, functionally cure HDV infection or HBV/HDV co-infection. This review summarizes our current knowledge of HBV molecular biology, presents an update on novel cell culture and animal models to study the virus and provides updates on the clinical development of the three developmental drugs Lonafarnib, REP2139-Ca and Myrcludex B.
Highlights
Hepatitis Delta Virus (HDV), the only member of the genus Deltavirus and the causative agent for chronic Hepatitis D (CHD), represents the smallest known animal virus and shows peculiar characteristics in both its morphology and replication cycle
This review summarizes our current knowledge of Hepatitis B Virus (HBV) molecular biology, presents an update on novel cell culture and animal models to study the virus and provides updates on the clinical development of the three developmental drugs Lonafarnib, REP2139-Ca and Myrcludex B
Before the discovery of the cellular receptor human sodium taurocholate cotransporting polypeptide (hNTCP), cell culture models for HDV were limited either to transfection based systems or infection of HepaRG cells and primary human hepatocytes (PHH), which are scarce in availability and show broad heterogeneity between donors [39,40,41]
Summary
Hepatitis Delta Virus (HDV), the only member of the genus Deltavirus and the causative agent for chronic Hepatitis D (CHD), represents the smallest known animal virus and shows peculiar characteristics in both its morphology and replication cycle. HDV is a satellite virus/virusoid of the human Hepatitis B Virus (HBV) as it requires the HBV envelope proteins (HBsAg) to form virus particles. HDV infection either establishes as a superinfection of an HBV-carrier or by simultaneous contact with HBV and HDV (see Table 1 for a characterization of both viruses). Discovered in 1977 [1], HDV is still a neglected pathogen, it causes the most severe form of viral hepatitis. About 15–20 million people worldwide are chronically infected with HDV, which is more than half the number of HIV-infected individuals.
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