Novel hepatitis D-like agents in vertebrates and invertebrates

Hepatitis delta virus (HDV) is the smallest known RNA virus and encodes a single protein. Until recently, HDV had only been identified in humans, where it is strongly associated with co-infection with hepatitis B virus (HBV). However, the recent discovery of HDV-like viruses in metagenomic samples from birds and snakes suggests that this virus has a far longer evolutionary history. Herein, using additional meta-transcriptomic data, we show that highly divergent HDV-like viruses are also present in fish, amphibians and invertebrates. Notably, the novel viruses identified here share HDV-like genomic features such as a small genome size of ~1.7kb in length, circular genomes, and self-complementary, unbranched rod-like structures. Coiled-coil domains, leucine zippers, conserved residues with essential biological functions and isoelectronic points similar to those in the human hepatitis delta virus antigens (HDAgs) were also identified in the putative non-human HDAgs. Notably, none of these novel HDV-like viruses were associated with hepadnavirus infection, supporting the idea that the HDV-HBV association may be specific to humans. Collectively, these data not only broaden our understanding of the diversity and host range of HDV in non-human species, but shed light on its origin and evolutionary history.

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A divergent hepatitis D-like agent in birds

10.1101/423707 ◽

2018 ◽

Cited By ~ 3

Author(s):

Michelle Wille ◽

Hans J. Netter ◽

Margaret Littlejohn ◽

Lilly Yuen ◽

Mang Shi ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Hepatitis Delta Virus ◽

Amino Acid Similarity ◽

Hepatitis Delta ◽

Hepatitis D ◽

Delta Antigen ◽

B Virus ◽

Severe Liver Disease ◽

Delta Virus

AbstractHepatitis delta virus (HDV) is currently only found in humans, and is a satellite virus that depends on hepatitis B virus (HBV) envelope proteins for assembly, release and entry. Using meta-transcriptomics, we identified the genome of a novel HDV-like agent in ducks. Sequence analysis revealed secondary structures that were shared with HDV, including self-complementarity and ribozyme features. The predicted viral protein shares 32% amino acid similarity to the small delta antigen of HDV and comprises a divergent phylogenetic lineage. The discovery of an avian HDV-like agent has important implications for the understanding of the origins of HDV and subviral agents.ImportanceHepatitis delta virus (HDV) is currently only found in humans, and coinfections of HDV and Hepatitis B virus (HBV) in humans result in severe liver disease. There are a number of hypotheses for the origin of HDV, although a key component of all is that HDV only exists in humans. Here, we describe a novel deltavirus-like agent identified in wild birds. Although this agent is genetically divergent, it exhibits important similarities to HDV, such as the presence of ribosymes and self-complementarity. The discovery of an avian HDV-like agent challenges our understanding of both the origin and the co-evolutionary relationships of subviral agents with helper viruses.

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Efficient Hepatitis Delta Virus RNA Replication in Avian Cells Requires a Permissive Factor(s) from Mammalian Cells

Journal of Virology ◽

10.1128/jvi.75.16.7489-7493.2001 ◽

2001 ◽

Vol 75 (16) ◽

pp. 7489-7493 ◽

Cited By ~ 5

Author(s):

Yu-Tsueng Liu ◽

Rob Brazas ◽

Don Ganem

Keyword(s):

Hepatitis Delta Virus ◽

Mammalian Cells ◽

Rna Virus ◽

Rna Replication ◽

Highly Pathogenic ◽

Hepatitis Delta ◽

Virus Rna ◽

B Virus ◽

Hdv Infection ◽

Delta Virus

ABSTRACT Hepatitis delta virus (HDV) is a highly pathogenic human RNA virus whose genome is structurally related to those of plant viroids. Although its spread from cell to cell requires helper functions supplied by hepatitis B virus (HBV), intracellular HDV RNA replication can proceed in the absence of HBV proteins. As HDV encodes no RNA-dependent RNA polymerase, the identity of the (presumably cellular) enzyme responsible for this reaction remains unknown. Here we show that, in contrast to mammalian cells, avian cells do not support efficient HDV RNA replication and that this defect cannot be rescued by provision of HDV gene products in trans. Contrary to earlier assertions, this defect is not due to enhanced apoptosis triggered in avian cells by HDV. Fusion of avian cells to mammalian cells rescues HDV replication in avian nuclei, indicating that the nonpermissive phenotype of avian cells is not due to the presence of dominantly acting inhibitors of replication. Rather, avian cells lack one or more essential permissive factors present in mammalian cells. These results set the stage for the identification of such factors and also explain the failure of earlier efforts to transmit HDV infection to avian hosts harboring indigenous hepadnaviruses.

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Hepatitis Delta Virus (HDV) and Delta-Like Agents: Insights Into Their Origin

Frontiers in Microbiology ◽

10.3389/fmicb.2021.652962 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hans J. Netter ◽

Marilou H. Barrios ◽

Margaret Littlejohn ◽

Lilly K. W. Yuen

Keyword(s):

Hepatitis Delta Virus ◽

Evolutionary History ◽

Circular Rna ◽

Circular Rnas ◽

Hepatitis Delta ◽

Delta Antigen ◽

B Virus ◽

Satellite Viruses ◽

Negative Sense ◽

Delta Virus

Hepatitis delta virus (HDV) is a human pathogen, and the only known species in the genus Deltavirus. HDV is a satellite virus and depends on the hepatitis B virus (HBV) for packaging, release, and transmission. Extracellular HDV virions contain the genomic HDV RNA, a single-stranded negative-sense and covalently closed circular RNA molecule, which is associated with the HDV-encoded delta antigen forming a ribonucleoprotein complex, and enveloped by the HBV surface antigens. Replication occurs in the nucleus and is mediated by host enzymes and assisted by cis-acting ribozymes allowing the formation of monomer length molecules which are ligated by host ligases to form unbranched rod-like circles. Recently, meta-transcriptomic studies investigating various vertebrate and invertebrate samples identified RNA species with similarities to HDV RNA. The delta-like agents may be representatives of novel subviral agents or satellite viruses which share with HDV, the self-complementarity of the circular RNA genome, the ability to encode a protein, and the presence of ribozyme sequences. The widespread distribution of delta-like agents across different taxa with considerable phylogenetic distances may be instrumental in comprehending their evolutionary history by elucidating the transition from transcriptome to cellular circular RNAs to infectious subviral agents.

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Analysis of Multiple Liver Explant Pieces Reveals that Levels of Hepatitis Delta Virus RNA Are Independent of Hepatitis B Virus Expression

Hepatology Communications ◽

10.1002/hep4.1764 ◽

2021 ◽

Author(s):

Kasthuri Prakash ◽

Simon B. Larsson ◽

Gustaf E. Rydell ◽

Johan Ringlander ◽

Catarina Skoglund ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Hepatitis Delta Virus ◽

Hepatitis Delta ◽

Virus Rna ◽

B Virus ◽

Virus Expression ◽

Delta Virus

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Occurrence of Hepatitis Delta Virus Infection in Hepatitis B Virus-Infected Patients with Different Serum Patterns of PreS Gene-Encoded Proteins

Digestion ◽

10.1159/000201004 ◽

1993 ◽

Vol 54 (1) ◽

pp. 9-14

Author(s):

Nicola Napoli ◽

Giorgio Fiore ◽

Giacomo Fera ◽

Angela Modugno ◽

Gianluigi Giannelli ◽

...

Keyword(s):

Hepatitis B Virus ◽

Virus Infection ◽

Hepatitis B ◽

Hepatitis Delta Virus ◽

Hepatitis Delta ◽

Hepatitis Delta Virus Infection ◽

B Virus ◽

Encoded Proteins ◽

Delta Virus

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A Divergent Hepatitis D-Like Agent in Birds

Viruses ◽

10.3390/v10120720 ◽

2018 ◽

Vol 10 (12) ◽

pp. 720 ◽

Cited By ~ 24

Author(s):

Michelle Wille ◽

Hans Netter ◽

Margaret Littlejohn ◽

Lilly Yuen ◽

Mang Shi ◽

...

Keyword(s):

Amino Acid ◽

Hepatitis B Virus ◽

Sequence Analysis ◽

Hepatitis B ◽

Hepatitis Delta Virus ◽

Amino Acid Similarity ◽

Hepatitis D ◽

Delta Antigen ◽

B Virus ◽

Delta Virus

Hepatitis delta virus (HDV) is currently only found in humans and is a satellite virus that depends on hepatitis B virus (HBV) envelope proteins for assembly, release, and entry. Using meta-transcriptomics, we identified the genome of a novel HDV-like agent in ducks. Sequence analysis revealed secondary structures that were shared with HDV, including self-complementarity and ribozyme features. The predicted viral protein shares 32% amino acid similarity to the small delta antigen of HDV and comprises a divergent phylogenetic lineage. The discovery of an avian HDV-like agent has important implications for the understanding of the origins of HDV and sub-viral agents.

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Delta hepatitis: molecular biology and clinical and epidemiological features.

Clinical Microbiology Reviews ◽

10.1128/cmr.6.3.211 ◽

1993 ◽

Vol 6 (3) ◽

pp. 211-229 ◽

Cited By ~ 30

Author(s):

L B Polish ◽

M Gallagher ◽

H A Fields ◽

S C Hadler

Keyword(s):

Liver Disease ◽

High Risk ◽

Hepatitis B ◽

Hepatitis Delta Virus ◽

Hepatitis B Infection ◽

Hepatitis Delta ◽

Hepatitis Delta Virus Infection ◽

B Virus ◽

The World ◽

Delta Virus

Hepatitis delta virus, discovered in 1977, requires the help of hepatitis B virus to replicate in hepatocytes and is an important cause of acute, fulminant, and chronic liver disease in many regions of the world. Because of the helper function of hepatitis delta virus, infection with it occurs either as a coinfection with hepatitis B or as a superinfection of a carrier of hepatitis B surface antigen. Although the mechanisms of transmission are similar to those of hepatitis B virus, the patterns of transmission of delta virus vary widely around the world. In regions of the world in which hepatitis delta virus infection is not endemic, the disease is confined to groups at high risk of acquiring hepatitis B infection and high-risk hepatitis B carriers. Because of the propensity of this viral infection to cause fulminant as well as chronic liver disease, continued incursion of hepatitis delta virus into areas of the world where persistent hepatitis B infection is endemic will have serious implications. Prevention depends on the widespread use of hepatitis B vaccine. This review focuses on the molecular biology and the clinical and epidemiologic features of this important viral infection.

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