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Abstract Details
Comprehensive Analysis of Hepatitis Delta Virus Assembly Determinants According to Genotypes: Lessons From a Study of 526 Hepatitis Delta Virus Clinical Strains
Front Microbiol. 2021 Nov 16;12:751531. doi: 10.3389/fmicb.2021.751531. eCollection 2021.
Athenaïs Gerber12, Frédéric Le Gal123, Samira Dziri12, Chakib Alloui123, Dominique Roulot234, Paul Dény15, Camille Sureau6, Ségolène Brichler123, Emmanuel Gordien123
Author information
Laboratoire de Microbiologie Clinique, Université Paris Nord, Sorbonne Paris Cité, Hôpitaux Universitaires de Paris-Seine-Saint-Denis, Bobigny, France.
Centre National de Référence des Hépatites B, C et Delta, Hôpitaux Universitaires de Paris-Seine-Saint-Denis, Bobigny, France.
INSERM U955, Équipe 18, Institut Mondor de Recherche Biomédicale, Créteil, France.
Unité d'Hépatologie, Université Paris Nord, Sorbonne Paris Cité, Hôpitaux Universitaires de Paris-Seine-Saint-Denis, Bobigny, France.
Inserm, U1052 - UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
Laboratoire de Virologie Moléculaire, Institut National de la Transfusion Sanguine, Paris, France.
Abstract
Human hepatitis Delta virus (HDV) infection is associated to the most severe viral hepatic disease, including severe acute liver decompensation and progression to cirrhosis, and hepatocellular carcinoma. HDV is a satellite of hepatitis B virus (HBV) that requires the HBV envelope proteins for assembly of HDV virions. HDV and HBV exhibit a large genetic diversity that extends, respectively to eight (HDV-1 to -8) and to ten (HBV/A to/J) genotypes. Molecular determinants of HDV virion assembly consist of a C-terminal Proline-rich domain in the large Hepatitis Delta Antigen (HDAg) protein, also known as the Delta packaging domain (DPD) and of a Tryptophan-rich domain, the HDV matrix domain (HMD) in the C-terminal region of the HBV envelope proteins. In this study, we performed a systematic genotyping of HBV and HDV in a cohort 1,590 HDV-RNA-positive serum samples collected between 2001 to 2014, from patients originated from diverse parts of the world, thus reflecting a large genetic diversity. Among these samples, 526 HBV (HBV/A, B, C, D, E, and G) and HDV (HDV-1, 2, 3, and 5 to -8) genotype couples could be obtained. We provide results of a comprehensive analysis of the amino-acid sequence conservation within the HMD and structural and functional features of the DPD that may account for the yet optimal interactions between HDV and its helper HBV.