Comprehensive Analysis of Hepatitis Delta Virus Assembly Determinants According to Genotypes: Lessons From a Study of 526 Hepatitis Delta Virus Clinical Strains

Frontiers in Microbiology

Samira Dziri¹  Athenaïs Gerber¹  Chakib Alloui²  Ségolène Brichler²  Emmanuel Gordien²  Frédéric Le Gal²  Paul Dény³  Camille Sureau⁵  Dominique Roulot⁶ 

[1] 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;Inserm, U1052 – UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France;Laboratoire de Microbiologie Clinique, Université Paris Nord, Sorbonne Paris Cité, Hôpitaux Universitaires de Paris-Seine-Saint-Denis, Bobigny, France;Laboratoire de Virologie Moléculaire, Institut National de la Transfusion Sanguine, Paris, France;Unité d’Hépatologie, Université Paris Nord, Sorbonne Paris Cité, Hôpitaux Universitaires de Paris-Seine-Saint-Denis, Bobigny, France;

关键词: HDV;    editing;    genotype;    HDAg;    next-generation-sequencing;    pathogenesis;   

DOI  :  10.3389/fmicb.2021.751531

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown