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

Athenaïs Gerber,Emmanuel Gordien,Ségolène Brichler,Camille Sureau,Samira Dziri,Frédéric Le Gal,Dominique Roulot,Chakib Alloui,Paul Dény

doi:10.3389/fmicb.2021.751531

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.

Highlights

The human Hepatitis Delta virus (HDV) is a satellite of hepatitis B virus (HBV), recruits the HBV envelope proteins for HDV virion assembly and, propagation
The determinants of HDV assembly on the RNP consists of a proline-rich domain (PRD) at the C-terminal region of L-HDV antigen (HDAg) named the Delta packaging domain (DPD) (Jenna and Sureau, 1998, 1999; Blanchet and Sureau, 2006; Komla-Soukha and Sureau, 2006; Dastgerdi et al, 2012; ShirvaniDastgerdi and Tacke, 2015) that includes a farnesylation signal that is crucial to virion assembly (Glenn et al, 1992; Bordier et al, 2003; Taylor, 2006)
HDV genotypes, such as African HDV-1 and HDV-5 to -8 originated from Africa, are found in European Eastern or Western countries, and European HDV-1 genotypes are observed in African patients, reflected migrations of populations

Summary

Introduction

The human Hepatitis Delta virus (HDV) is a satellite of hepatitis B virus (HBV), recruits the HBV envelope proteins for HDV virion assembly and, propagation. Hepatitis delta virus is responsible for the most severe viral hepatitis, and chronically infected individuals may progress to liver fibrosis, cirrhosis decompensation and hepatocellular carcinoma (HCC). The determinants of HDV assembly on the RNP consists of a proline-rich domain (PRD) at the C-terminal region of L-HDAg named the Delta packaging domain (DPD) (Jenna and Sureau, 1998, 1999; Blanchet and Sureau, 2006; Komla-Soukha and Sureau, 2006; Dastgerdi et al, 2012; ShirvaniDastgerdi and Tacke, 2015) that includes a farnesylation signal that is crucial to virion assembly (Glenn et al, 1992; Bordier et al, 2003; Taylor, 2006). We analyzed the conservation of the HDV assembly determinants using a panel of 1,590 HDV-RNA-positive serum samples collected between 2001 to 2014 by the French National Reference Centre for Viral Hepatitis B, C, and D (FNRC-D), according to HBV and HDV genotypes. We performed a systematic HBV and HDV genotyping and carefully analyzed the aminoacid sequences of the HDV assembly determinants

Methods

Results

Conclusion