scholarly journals Constraint of Base Pairing on HDV Genome Evolution

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2350
Author(s):  
Saki Nagata ◽  
Ryoji Kiyohara ◽  
Hiroyuki Toh
Keyword(s):  
Hepatitis Delta Virus ◽  
Evolutionary Rate ◽  
Rna Virus ◽  
Circular Rna ◽  
Coding Region ◽  
Base Pairing ◽  
Nucleotide Substitutions ◽  
Base Pairs ◽  
Hepatitis Delta ◽  
Delta Virus

The hepatitis delta virus is a single-stranded circular RNA virus, which is characterized by high self-complementarity. About 70% of the genome sequences can form base-pairs with internal nucleotides. There are many studies on the evolution of the hepatitis delta virus. However, the secondary structure has not been taken into account in these studies. In this study, we developed a method to examine the effect of base pairing as a constraint on the nucleotide substitutions during the evolution of the hepatitis delta virus. The method revealed that the base pairing can reduce the evolutionary rate in the non-coding region of the virus. In addition, it is suggested that the non-coding nucleotides without base pairing may be under some constraint, and that the intensity of the constraint is weaker than that by the base pairing but stronger than that on the synonymous site.

scholarly journals Novel hepatitis D-like agents in vertebrates and invertebrates

2019 ◽  
Author(s):  
Wei-Shan Chang ◽  
John H.-O. Pettersson ◽  
Callum Le Lay ◽  
Mang Shi ◽  
Nathan Lo ◽  
...  
Keyword(s):  
Hepatitis Delta Virus ◽  
Evolutionary History ◽  
Rna Virus ◽  
Coiled Coil ◽  
The Novel ◽  
Leucine Zippers ◽  
Hepatitis Delta ◽  
Hepatitis D ◽  
B Virus ◽  
Delta Virus

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.

scholarly journals Effects of Conserved RNA Secondary Structures on Hepatitis Delta Virus Genotype I RNA Editing, Replication, and Virus Production

2005 ◽  
Vol 79 (17) ◽  
pp. 11187-11193 ◽  
Author(s):  
Geetha C. Jayan ◽  
John L. Casey
Keyword(s):  
Secondary Structure ◽  
Rna Editing ◽  
Hepatitis Delta Virus ◽  
Virus Production ◽  
Rna Replication ◽  
Base Pairing ◽  
Genotype I ◽  
Hepatitis Delta ◽  
Hdv Genotype ◽  
Delta Virus

ABSTRACT RNA editing of the hepatitis delta virus (HDV) antigenome at the amber/W site by the host RNA adenosine deaminase ADAR1 is a critical step in the HDV replication cycle. Editing is required for production of the viral protein hepatitis delta antigen long form (HDAg-L), which is necessary for viral particle production but can inhibit HDV RNA replication. The RNA secondary structural features in ADAR1 substrates are not completely defined, but base pairing in the 20-nucleotide (nt) region 3′ of editing sites is thought to be important. The 25-nt region 3′ of the HDV amber/W site in HDV genotype I RNA consists of a conserved secondary structure that is mostly base paired but also has asymmetric internal loops and single-base bulges. To understand the effect of this 3′ region on the HDV replication cycle, mutations that either increase or decrease base pairing in this region were created and the effects of these changes on amber/W site editing, RNA replication, and virus production were studied. Increased base pairing, particularly in the region 15 to 25 nt 3′ of the editing site, significantly increased editing; disruption of base pairing in this region had little effect. Increased editing resulted in a dramatic inhibition of HDV RNA synthesis, mostly due to excess HDAg-L production. Although virus production at early times was unaffected by this reduced RNA replication, at later times it was significantly reduced. Therefore, it appears that the conserved RNA secondary structure around the HDV genotype I amber/W site has been selected not for the highest editing efficiency but for optimal viral replication and secretion.

scholarly journals Characterization of the 5′ Ends for Polyadenylated RNAs Synthesized during the Replication of Hepatitis Delta Virus

1999 ◽  
Vol 73 (8) ◽  
pp. 6533-6539 ◽  
Author(s):  
Severin Gudima ◽  
Kate Dingle ◽  
Ting-Ting Wu ◽  
Gloria Moraleda ◽  
John Taylor
Keyword(s):  
Transcription Initiation ◽  
Hepatitis Delta Virus ◽  
Circular Rna ◽  
Genome Replication ◽  
Genomic Rna ◽  
Experimental Conditions ◽  
Hepatitis Delta ◽  
Polyadenylated Rnas ◽  
Delta Virus

ABSTRACT The genome of hepatitis delta virus (HDV) is a 1,679-nucleotide (nt) single-stranded circular RNA that is predicted to fold into an unbranched rodlike structure. During replication, two complementary RNAs are also detected: an exact complement, referred to as the antigenome, and an 800-nt polyadenylated RNA that could act as the mRNA for the delta antigen. We used a 5′ rapid amplification of cDNA ends procedure, followed by cloning and sequencing, to determine the 5′ ends of the polyadenylated RNAs produced during HDV genome replication following initiation under different experimental conditions. The analyzed RNAs were from the liver of an infected woodchuck and from a liver cell line at 6 days after transfection with either an HDV cDNA or ribonucleoprotein (RNP) complexes assembled in vitro with HDV genomic RNA and purified recombinant small delta protein. In all three situations the 5′ ends mapped specifically to nt 1630. In relationship to what is called the top end of the unbranched rodlike structure predicted for the genomic RNA template, this site is located 10 nt from the top, and in the middle of a 3-nt external bulge. Following transfection with RNP, such specific 5′ ends could be detected as early as 24 h. We next constructed a series of mutants of this predicted bulge region and of an adjacent 6-bp stem and the top 5-nt loop. Some of these mutations decreased the ability of the genome to undergo antigenomic RNA synthesis and accumulation and/or altered the location of the detected 5′ ends. The observed end located at nt 1630, and most of the novel 5′ ends, were consistent with transcription initiation events that preferentially used a purine. The present studies do not prove that the detected 5′ ends correspond to initiation sites and do not establish the hypothesis that there is a promoter element in the vicinity, but they do show that the location of the observed 5′ ends could be controlled by nucleotide sequences at and around nt 1630.

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

2001 ◽  
Vol 75 (16) ◽  
pp. 7489-7493 ◽  
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.

scholarly journals Hepatitis Delta Virus: A Peculiar Virus

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Carolina Alves ◽  
Cristina Branco ◽  
Celso Cunha
Keyword(s):  
Hepatitis Delta Virus ◽  
Rna Virus ◽  
Severe Form ◽  
Satellite Rna ◽  
Hepatitis Delta ◽  
Human Virus ◽  
Biological Features ◽  
Hepatitis B Surface Antigens ◽  
Available Information ◽  
Delta Virus

The hepatitis delta virus (HDV) is distributed worldwide and related to the most severe form of viral hepatitis. HDV is a satellite RNA virus dependent on hepatitis B surface antigens to assemble its envelope and thus form new virions and propagate infection. HDV has a small 1.7 Kb genome making it the smallest known human virus. This deceivingly simple virus has unique biological features and many aspects of its life cycle remain elusive. The present review endeavors to gather the available information on HDV epidemiology and clinical features as well as HDV biology.

scholarly journals Evolution of Hepatitis Delta Virus RNA Genome following Long-Term Replication in Cell Culture

2005 ◽  
Vol 79 (21) ◽  
pp. 13310-13316 ◽  
Author(s):  
Jinhong Chang ◽  
Severin O. Gudima ◽  
John M. Taylor
Keyword(s):  
Cell Culture ◽  
Hepatitis Delta Virus ◽  
Experimental System ◽  
Genome Replication ◽  
Nucleotide Substitutions ◽  
Single Nucleotide ◽  
Hepatitis Delta ◽  
Rna Genome ◽  
Nucleotide Insertions ◽  
Delta Virus

ABSTRACTPrevious studies have defined a novel cell culture system in which a modified RNA genome of hepatitis delta virus (HDV) is able to maintain a low level of continuous replication for at least 1 year, using a separate and limited DNA-directed source of mRNA for the essential small delta protein. This mode of replication is analogous to that used by plant viroids. An examination was made of the nucleotide changes that accumulated on the HDV RNA during 1 year of replication. The length of the RNA genome was maintained, except for some single-nucleotide deletions and insertions. There was an abundance of single-nucleotide substitutions, with a 22-fold excess of these being base transitions rather than transversions. Of the detected transitions, at least 70% were consistent with being the consequences of posttranscriptional RNA editing by an adenosine deaminase acting on RNA. The remainder of the changes, including the single-nucleotide insertions and deletions, are likely to be the consequence of misincorporation during transcription. In addition, an intermolecular competition assay was used to show that the majority of the genomes present after 1 year of replication were essentially as competent in replication as the original single HDV RNA sequence that was used to initiate the genome replication. A model is provided to explain how, in this experimental system, the observed single-nucleotide changes were essentially neutral in terms of their effect on the ability of the HDV genome to carry out continued rounds of replication.

scholarly journals Structural Pattern Differences in Unbranched Rod-like RNA of Hepatitis Delta Virus affect RNA Editing

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 934 ◽  
Author(s):  
Hsu ◽  
Juang ◽  
Kuo ◽  
Li ◽  
Iang ◽  
...  
Keyword(s):  
Rna Editing ◽  
Rna Structure ◽  
Hepatitis Delta Virus ◽  
Rna Structures ◽  
Base Pairing ◽  
Hepatitis Delta ◽  
Virion Assembly ◽  
Editing Efficiency ◽  
Naturally Occurring ◽  
Delta Virus

Hepatitis delta virus (HDV) RNA forms an unbranched rod-like structure and complexes with the delta antigen (HDAg). Host ADAR1-catalyzed RNA editing at the amber/W site of the small HDAg leads to the production of the large HDAg, which inhibits replication and is required for virion assembly. For HDV genotype 1, amber/W editing is controlled by HDAg and the RNA structure immediate vicinity and downstream of the editing site. Here, the effects of 20 mutants carrying an increased length of consecutive base-pairing at various sites in HDV RNA on amber/W site editing were examined. All nine mutants carrying genomic regions that formed up to 15 consecutive base pairs, which is also the maximum length observed in 41 naturally occurring HDV genomes, showed normal editing rate. However, mutants carrying a 16 or 17 consecutive base-paired antigenomic segment located as far as 114 nt upstream could increase editing efficiency, possibly by interfering with HDAg binding. These data show for the first time that extended base-pairing upstream of the amber/W site could increase HDV RNA editing efficiency. Furthermore, it appears that the naturally occurring HDV RNA structures have been selected for suboptimal amber/W RNA editing, which favors the HDV replication cycle.

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

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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