Cellular Factors Involved in the Hepatitis D Virus Life Cycle

Abstract

Hepatitis D virus (HDV) is a defective RNA virus with a negative-strand RNA genome encompassing less than 1700 nucleotides. The HDV genome encodes only for one protein, the hepatitis delta antigen (HDAg), which exists in two forms acting as nucleoproteins. HDV depends on the envelope proteins of the hepatitis B virus as a helper virus for packaging its ribonucleoprotein complex (RNP). HDV is considered the causative agent for the most severe form of viral hepatitis leading to liver fibrosis/cirrhosis and hepatocellular carcinoma. Many steps of the life cycle of HDV are still enigmatic. This review gives an overview of the complete life cycle of HDV and identifies gaps in knowledge. The focus is on the description of cellular factors being involved in the life cycle of HDV and the deregulation of cellular pathways by HDV with respect to their relevance for viral replication, morphogenesis and HDV-associated pathogenesis. Moreover, recent progress in antiviral strategies targeting cellular structures is summarized in this article.

Highlights from the 2023 International Meeting on the Molecular Biology of Hepatitis B virus

“…An estimated 15 million people worldwide are chronically infected with HDV and HBV and this co-infection is associated with a higher risk of severe hepatitis, cirrhosis, and HCC [15]. Gaps remain in our knowledge of cellular factors required for HDV replication and HDV regulation of host factors, as well as the interactions between HDV and HBV in the setting of coinfection (reviewed in [16]).…”