Acute Hepatitis D (HDV)

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Characteristics|epidemiology

Hepatitis delta virus (HDV) is not related to any other human or animal virus. HDV more or less parasitizes HBV, because it uses the envelope of HBV as an envelope. Infection with HDV is therefore only possible in the presence of infection with HBV.

Sporadic cases of HDV infection occur worldwide. The virus is found relatively often in intravenous drug users. HDV spreads mainly through blood-to-blood contact.

Hepatitis Delta virus life cycle HDV is the smallest human infecting virus and the sole member of the Deltavirus genus. HDV is characterized as a “satellite” or “defective” virus as it is dependent on HBV co-infection for viral assembly and persistence. HDV has an approximate 1.7 kb circular, single-stranded, negative-sense RNA genome that encodes for a single protein of two isoforms: The small and large delta antigens (S-HDAg and L-HDAg, respectively). Viral entry occurs similarly to HBV due to HDV’s co-opted use of the envelope HBsAg protein. Following viral entry, HDV uncoats in the cytoplasm and the ribonucleoprotein complex consisting of the HDV viral genome and HDAg complex is imported into the nucleus. Rolling-circle replication occurs in the nucleolus using the host RNA polymerase II to produce antigenomic positive sense HDV RNA that serves as a template for genomic HDV RNA synthesis and protein production. The antigenome can be edited by host protein adenosine deaminase acting on RNA 1 (ADAR1) to change adenine to inosine in the UAG stop-codon to produce the L-HDAg. The edited and non-edited antigenomes are then linearized by the HDV associated ribozyme, exported to the cytoplasm, and translated to HDV antigens. The non-edited transcript produces S-HDAg (24 kDa) and the transcript modified by ADAR1 produces the L-HDAg (27 kDa). Following extensive post-translational modifications, the viral antigens associate with the HDV RNA in the cytoplasm to form the ribonucleoprotein complex. The ribonucleoprotein is trafficked through the ER and Golgi apparatus where it co-opts the HBsAg envelope produced by HBV, and then buds out of the cell.

D'souza S, Lau KCK, Coffin CS, Patel TR. Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma. World J Gastroenterol 2020; 26(38): 5759-5783 [PMID: PMC7579760 DOI: 10.3748/wjg.v26.i38.5759] 

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