scholarly journals Identification of novel avian and mammalian deltaviruses provides new insights into deltavirus evolution

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Masashi Iwamoto ◽  
Yukino Shibata ◽  
Junna Kawasaki ◽  
Shohei Kojima ◽  
Yung-Tsung Li ◽  
...  
Keyword(s):  
Hepatitis Delta Virus ◽  
Envelope Proteins ◽  
Interspecies Transmission ◽  
Passerine Birds ◽  
Molecular Surveillance ◽  
Hepatitis Delta ◽  
The Past ◽  
Satellite Virus ◽  
Experimental Analyses ◽  
Delta Virus

Abstract Hepatitis delta virus (HDV) is a satellite virus that requires hepadnavirus envelope proteins for its transmission. Although recent studies identified HDV-related deltaviruses in certain animals, the evolution of deltaviruses, such as the origin of HDV and the mechanism of its coevolution with its helper viruses, is unknown, mainly because of the phylogenetic gaps among deltaviruses. Here, we identified novel deltaviruses of passerine birds, woodchucks, and white-tailed deer by extensive database searches and molecular surveillance. Phylogenetic and molecular epidemiological analyses suggest that HDV originated from mammalian deltaviruses and the past interspecies transmission of mammalian and passerine deltaviruses. Further, metaviromic and experimental analyses suggest that the satellite–helper relationship between HDV and hepadnavirus was established after the divergence of the HDV lineage from non-HDV mammalian deltaviruses. Our findings enhance our understanding of deltavirus evolution, diversity, and transmission, indicating the importance of further surveillance for deltaviruses.

scholarly journals Identification of novel avian and mammalian deltaviruses provides new insights into deltavirus evolution

2020 ◽  
Author(s):  
Masashi Iwamoto ◽  
Yukino Shibata ◽  
Junna Kawasaki ◽  
Shohei Kojima ◽  
Yung-Tsung Li ◽  
...  
Keyword(s):  
Hepatitis Delta Virus ◽  
Envelope Proteins ◽  
Interspecies Transmission ◽  
Passerine Birds ◽  
Molecular Surveillance ◽  
Hepatitis Delta ◽  
The Past ◽  
Satellite Virus ◽  
Experimental Analyses ◽  
Delta Virus

AbstractHepatitis delta virus (HDV) is a satellite virus that requires hepadnavirus envelope proteins for its transmission. Although recent studies identified HDV-related deltaviruses in certain animals, the evolution of deltaviruses, such as the origin of HDV and the mechanism of its coevolution with its helper viruses, is unknown, mainly because of the phylogenetic gaps among deltaviruses. Here we identified novel deltaviruses of passerine birds, woodchucks, and white-tailed deer by extensive database searches and molecular surveillance. Phylogenetic and molecular epidemiological analyses suggest that HDV originated from mammalian deltaviruses and the past interspecies transmission of mammalian and passerine deltaviruses. Further, metaviromic and experimental analyses suggest that the satellite-helper relationship between HDV and hepadnavirus was established after the divergence of the HDV lineage from non-HDV mammalian deltaviruses. Our findings enhance our understanding of deltavirus evolution, diversity, and transmission, indicating the importance of further surveillance for deltaviruses.

scholarly journals Role of N Glycosylation of Hepatitis B Virus Envelope Proteins in Morphogenesis and Infectivity of Hepatitis Delta Virus

2003 ◽  
Vol 77 (9) ◽  
pp. 5519-5523 ◽  
Author(s):  
Camille Sureau ◽  
Chantal Fournier-Wirth ◽  
Patrick Maurel
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis Delta Virus ◽  
Envelope Proteins ◽  
Virus Envelope ◽  
Hepatitis Delta ◽  
B Virus ◽  
L Proteins ◽  
Delta Virus

ABSTRACT Hepatitis delta virus (HDV) particles are coated with the large (L), middle (M), and small (S) hepatitis B virus envelope proteins. In the present study, we constructed glycosylation-defective envelope protein mutants and evaluated their capacity to assist in the maturation of infectious HDV in vitro. We observed that the removal of N-linked carbohydrates on the S, M, and L proteins was tolerated for the assembly of subviral hepatitis B virus (HBV) particles but was partially inhibitory for the formation of HDV virions. However, when assayed on primary cultures of human hepatocytes, virions coated with S, M, and L proteins lacking N-linked glycans were infectious. Furthermore, in the absence of M, HDV particles coated with nonglycosylated S and L proteins retained infectivity. These results indicate that carbohydrates on the HBV envelope proteins are not essential for the in vitro infectivity of HDV.

scholarly journals Nucleic acid polymers are active against Hepatitis Delta Virus infection in vitro.

2017 ◽  
pp. JVI.01416-17 ◽  
Author(s):  
Frauke Beilstein ◽  
Matthieu Blanchet ◽  
Andrew Vaillant ◽  
Camille Sureau
Keyword(s):  
Nucleic Acid ◽  
Viral Entry ◽  
Hepatitis Delta Virus ◽  
Immune Escape ◽  
Envelope Proteins ◽  
Infection Model ◽  
Hepatitis Delta ◽  
Hdv Infection ◽  
Delta Virus

In this study, an in vitro infection model for the hepatitis delta virus (HDV) was used to evaluate the antiviral effects of phosphorothioate nucleic acid polymers (NAPs) and investigate their mechanism of action. The results show that NAPs inhibit HDV infection at less than 4 micromolar concentrations in cultures of differentiated human hepatoma cells. NAPs were shown to be active at viral entry, but inactive post entry on HDV RNA replication. Inhibition was independent of the NAPs nucleotide sequence, but dependent on both size and amphipathicity of the polymer. NAPs antiviral activity was effective against HDV virions bearing the main hepatitis B virus (HBV) immune escape substitutions (D144A and G145R) and was pangenomic with regard to HBV envelope proteins. Furthermore, similar to immobilized heparin, immobilized NAPs could bind HDV particles suggesting that entry inhibition was due, at least in part, to preventing attachment of the virus to cell surface glycosaminoglycans. The results document NAPs as a novel class of antiviral compounds that can prevent HDV propagation.IMPORTANCEHDV infection causes the most severe form of viral hepatitis in humans and one of the most difficult to cure. Currently, treatments are limited to long-term administration of interferon at high doses, which provide only partial efficacy. There is thus an urgent need for innovative approaches to identify new antiviral against HDV. The significance of our study is in demonstrating that nucleic acid polymers (NAPs) are active against HDV by targeting the envelope of HDV virions. In an in vitro infection assay, NAPs activity was recorded at less than 4 micromolar concentrations in the absence of cell toxicity. Furthermore, the fact that NAPs could block HDV at viral entry, suggest their potential to control the spread of HDV in a chronically HBV-infected liver. In addition, NAPs anti-HDV activity was pangenomic with regard to HBV envelope proteins and not circumvented by HBsAg substitutions associated with HBV immune escape.

scholarly journals Assembly of Hepatitis Delta Virus: Particle Characterization, Including the Ability To Infect Primary Human Hepatocytes

2007 ◽  
Vol 81 (7) ◽  
pp. 3608-3617 ◽  
Author(s):  
Severin Gudima ◽  
Yiping He ◽  
Anja Meier ◽  
Jinhong Chang ◽  
Rongji Chen ◽  
...  
Keyword(s):  
Hepatitis Delta Virus ◽  
Envelope Proteins ◽  
Human Hepatocytes ◽  
Cell Junctions ◽  
Host Cells ◽  
Hepatitis Delta ◽  
Primary Human Hepatocytes ◽  
Natural Helper ◽  
Huh7 Cells ◽  
Delta Virus

ABSTRACT Efficient assembly of hepatitis delta virus (HDV) was achieved by cotransfection of Huh7 cells with two plasmids: one to provide expression of the large, middle, and small envelope proteins of hepatitis B virus (HBV), the natural helper of HDV, and another to initiate replication of the HDV RNA genome. HDV released into the media was assayed for HDV RNA and HBV envelope proteins and characterized by rate-zonal sedimentation, immunoaffinity purification, electron microscopy, and the ability to infect primary human hepatocytes. Among the novel findings were that (i) immunostaining for delta antigen 6 days after infection with 300 genome equivalents (GE) per cell showed only 1% of cells as infected, but this was increased to 16% when 5% polyethylene glycol was present during infection; (ii) uninfected cells did not differ from infected cells in terms of albumin accumulation or the presence of E-cadherin at cell junctions; and (iii) sensitive quantitative real-time PCR assays detected HDV replication even when the multiplicity of infection was 0.2 GE/cell. In the future, this HDV assembly and infection system can be further developed to better understand the mechanisms shared by HBV and HDV for attachment and entry into host cells.

scholarly journals Primary Human Hepatocytes Are Susceptible to Infection by Hepatitis Delta Virus Assembled with Envelope Proteins of Woodchuck Hepatitis Virus

2008 ◽  
Vol 82 (15) ◽  
pp. 7276-7283 ◽  
Author(s):  
Severin Gudima ◽  
Yiping He ◽  
Ning Chai ◽  
Volker Bruss ◽  
Stephan Urban ◽  
...  
Keyword(s):  
Host Range ◽  
Hepatitis Delta Virus ◽  
Hepatitis Virus ◽  
Envelope Proteins ◽  
Human Hepatocytes ◽  
Target Cells ◽  
Woodchuck Hepatitis Virus ◽  
Hepatitis Delta ◽  
Primary Human Hepatocytes ◽  
Delta Virus

ABSTRACT Hepatitis B virus (HBV) and hepatitis delta virus (HDV) share the HBV envelope proteins. When woodchucks chronically infected with woodchuck hepatitis virus (WHV) are superinfected with HDV, they produce HDV with a WHV envelope, wHDV. Several lines of evidence are provided that wHDV infects not only cultured primary woodchuck hepatocytes (PWH) but also primary human hepatocytes (PHH). Surprisingly, HBV-enveloped HDV (hHDV) and wHDV infected PHH with comparable efficiencies; however, hHDV did not infect PWH. The basis for these host range specificities was investigated using as inhibitors peptides bearing species-specific pre-S (where S is the small envelope protein) sequences. It was found that pre-S1 contributed to the ability of wHDV to infect both PHH and PWH. In addition, the inability of hHDV to infect PWH was not overcome using a chimeric form of hHDV containing WHV S protein, again supporting the essential role of pre-S1 in infection of target cells. One interpretation of these data is that host range specificity of HDV is determined entirely by pre-S1 and that the WHV and HBV pre-S1 proteins recognize different receptors on PHH.

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

2021 ◽  
Vol 12 ◽  
Author(s):  
Athenaïs Gerber ◽  
Frédéric Le Gal ◽  
Samira Dziri ◽  
Chakib Alloui ◽  
Dominique Roulot ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Hepatitis Delta Virus ◽  
Virus Assembly ◽  
Envelope Proteins ◽  
Comprehensive Analysis ◽  
Serum Samples ◽  
Hepatitis Delta ◽  
Rich Domain ◽  
Functional Features ◽  
Delta Virus

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.

scholarly journals Role of the Antigenic Loop of the Hepatitis B Virus Envelope Proteins in Infectivity of Hepatitis Delta Virus

2005 ◽  
Vol 79 (16) ◽  
pp. 10460-10466 ◽  
Author(s):  
Georges Abou Jaoudé ◽  
Camille Sureau
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Viral Entry ◽  
Hepatitis Delta Virus ◽  
Envelope Proteins ◽  
Single Amino Acid ◽  
Hepatitis Delta ◽  
B Virus ◽  
Virion Surface ◽  
Delta Virus

ABSTRACT The infectious particles of hepatitis B virus (HBV) and hepatitis delta virus (HDV) are coated with the large, middle, and small envelope proteins encoded by HBV. While it is clear that the N-terminal pre-S1 domain of the large protein, which is exposed at the virion surface, is implicated in binding to a cellular receptor at viral entry, the role in infectivity of the envelope protein antigenic loop, also exposed to the virion surface and accessible to neutralizing antibodies, remains to be established. In the present study, mutations were created in the antigenic loop of the three envelope proteins, and the resulting mutants were evaluated for their capacity to assist in the maturation and infectivity of HDV. We observed that short internal combined deletions and insertions, affecting residues 109 to 133 in the antigenic loop, were tolerated for secretion of both subviral HBV particles and HDV virions. However, when assayed for infectivity on primary cultures of human hepatocytes or on the recently described HepaRG cell line, virions carrying deletions between residues 118 and 129 were defective. Single amino acid substitutions in this region revealed that Gly-119, Pro-120, Cys-121, Arg-122, and Cys-124 were instrumental in viral entry. These results demonstrate that in addition to a receptor-binding site previously identified in the pre-S1 domain of the L protein, a determinant of infectivity resides in the antigenic loop of HBV envelope proteins.

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