scholarly journals RNA Editing in Hepatitis Delta Virus: Unsolved Puzzles

2004 ◽  
Vol 4 ◽  
pp. 628-637 ◽  
Author(s):  
Geetha C. Jayan
Keyword(s):  
Rna Editing ◽  
Hepatitis Delta Virus ◽  
Rna Virus ◽  
Regulation Of Gene Expression ◽  
Hepatitis Delta ◽  
Adenosine Deaminases ◽  
Different Types ◽  
Important Player ◽  
Transcriptional Changes ◽  
Delta Virus

RNA editing, or post-transcriptional changes in the sequences of RNAs, is being increasingly recognized as an important player in the regulation of gene expression in vertebrates and invertebrates. Different types of RNA editing have been reported. This review discuss the type of RNA editing caused by cellular enzymes known as adenosine deaminases that act on RNAs (ADARs), and it's significance in the lifecycle of an RNA virus, hepatitis delta virus.

scholarly journals Hepatitis Delta Virus RNA Editing Is Highly Specific for the Amber/W Site and Is Suppressed by Hepatitis Delta Antigen

1998 ◽  
Vol 18 (4) ◽  
pp. 1919-1926 ◽  
Author(s):  
Andrew G. Polson ◽  
Herbert L. Ley ◽  
Brenda L. Bass ◽  
John L. Casey
Keyword(s):  
Rna Editing ◽  
Hepatitis Delta Virus ◽  
Hepatitis Delta ◽  
Reading Frame ◽  
Adenosine Deaminases ◽  
Delta Antigen ◽  
Virus Rna ◽  
Hepatitis Delta Antigen ◽  
Delta Virus

ABSTRACT RNA editing at adenosine 1012 (amber/W site) in the antigenomic RNA of hepatitis delta virus (HDV) allows two essential forms of the viral protein, hepatitis delta antigen (HDAg), to be synthesized from a single open reading frame. Editing at the amber/W site is thought to be catalyzed by one of the cellular enzymes known as adenosine deaminases that act on RNA (ADARs). In vitro, the enzymes ADAR1 and ADAR2 deaminate adenosines within many different sequences of base-paired RNA. Since promiscuous deamination could compromise the viability of HDV, we wondered if additional deamination events occurred within the highly base paired HDV RNA. By sequencing cDNAs derived from HDV RNA from transfected Huh-7 cells, we determined that the RNA was not extensively modified at other adenosines. Approximately 0.16 to 0.32 adenosines were modified per antigenome during 6 to 13 days posttransfection. Interestingly, all observed non-amber/W adenosine modifications, which occurred mostly at positions that are highly conserved among naturally occurring HDV isolates, were found in RNAs that were also modified at the amber/W site. Such coordinate modification likely limits potential deleterious effects of promiscuous editing. Neither viral replication nor HDAg was required for the highly specific editing observed in cells. However, HDAg was found to suppress editing at the amber/W site when expressed at levels similar to those found during HDV replication. These data suggest HDAg may regulate amber/W site editing during virus replication.

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 Hepatitis Delta Virus Minimal Substrates Competent for Editing by ADAR1 and ADAR2

2001 ◽  
Vol 75 (18) ◽  
pp. 8547-8555 ◽  
Author(s):  
Shuji Sato ◽  
Swee Kee Wong ◽  
David W. Lazinski
Keyword(s):  
Hepatitis Delta Virus ◽  
Cultured Cells ◽  
Reporter System ◽  
Editing Event ◽  
Hepatitis Delta ◽  
Reading Frame ◽  
Adenosine Deaminases ◽  
Delta Antigen ◽  
Amber Codon ◽  
Delta Virus

ABSTRACT A host-mediated RNA-editing event allows hepatitis delta virus (HDV) to express two essential proteins, the small delta antigen (HDAg-S) and the large delta antigen (HDAg-L), from a single open reading frame. One or several members of the ADAR (adenosine deaminases that act on RNA) family are thought to convert the adenosine to an inosine (I) within the HDAg-S amber codon in antigenomic RNA. As a consequence of replication, the UIG codon is converted to a UGG (tryptophan [W]) codon in the resulting HDAg-L message. Here, we used a novel reporter system to monitor the editing of the HDV amber/W site in the absence of replication. In cultured cells, we observed that both human ADAR1 (hADAR1) and hADAR2 were capable of editing the amber/W site with comparable efficiencies. We also defined the minimal HDV substrate required for hADAR1- and hADAR2-mediated editing. Only 24 nucleotides from the amber/W site were sufficient to enable efficient editing by hADAR1. Hence, the HDV amber/W site represents the smallest ADAR substrate yet identified. In contrast, the minimal substrate competent for hADAR2-mediated editing contained 66 nucleotides.

scholarly journals RNA Editing and its Control in Hepatitis Delta Virus Replication

Viruses ◽  
2010 ◽  
Vol 2 (1) ◽  
pp. 131-146 ◽  
Author(s):  
Renxiang Chen ◽  
Sarah Linnstaedt ◽  
John Casey
Keyword(s):  
Rna Editing ◽  
Virus Replication ◽  
Hepatitis Delta Virus ◽  
Hepatitis Delta ◽  
Delta Virus

RNA editing of hepatitis delta virus antigenome by dsRNA-adenosine deaminase

Nature ◽  
1996 ◽  
Vol 380 (6573) ◽  
pp. 454-456 ◽  
Author(s):  
Andrew G. Poison ◽  
Brenda L. Bass ◽  
John L. Casey
Keyword(s):  
Adenosine Deaminase ◽  
Rna Editing ◽  
Hepatitis Delta Virus ◽  
Hepatitis Delta ◽  
Delta Virus

scholarly journals Increased RNA Editing and Inhibition of Hepatitis Delta Virus Replication by High-Level Expression of ADAR1 and ADAR2

2002 ◽  
Vol 76 (8) ◽  
pp. 3819-3827 ◽  
Author(s):  
Geetha C. Jayan ◽  
John L. Casey
Keyword(s):  
Rna Editing ◽  
Hepatitis Delta Virus ◽  
Rna Replication ◽  
Rna Packaging ◽  
High Level Expression ◽  
Hepatitis Delta ◽  
Huh7 Cells ◽  
Hepatitis Delta Antigen ◽  
High Level ◽  
Delta Virus

ABSTRACT Hepatitis delta virus (HDV) is a subviral human pathogen that uses specific RNA editing activity of the host to produce two essential forms of the sole viral protein, hepatitis delta antigen (HDAg). Editing at the amber/W site of HDV antigenomic RNA leads to the production of the longer form (HDAg-L), which is required for RNA packaging but which is a potent trans-dominant inhibitor of HDV RNA replication. Editing in infected cells is thought to be catalyzed by one or more of the cellular enzymes known as adenosine deaminases that act on RNA (ADARs). We examined the effects of increased ADAR1 and ADAR2 expression on HDV RNA editing and replication in transfected Huh7 cells. We found that both ADARs dramatically increased RNA editing, which was correlated with strong inhibition of HDV RNA replication. While increased HDAg-L production was the primary mechanism of inhibition, we observed at least two additional means by which ADARs can suppress HDV replication. High-level expression of both ADAR1 and ADAR2 led to extensive hyperediting at non-amber/W sites and subsequent production of HDAg variants that acted as trans-dominant inhibitors of HDV RNA replication. Moreover, we also observed weak inhibition of HDV RNA replication by mutated forms of ADARs defective for deaminase activity. Our results indicate that HDV requires highly regulated and selective editing and that the level of ADAR expression can play an important role: overexpression of ADARs inhibits HDV RNA replication and compromises virus viability.

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.

RNA editing in the replication cycle of human hepatitis delta virus

Biochimie ◽  
1994 ◽  
Vol 76 (12) ◽  
pp. 1205-1208 ◽  
Author(s):  
T.T. Wu ◽  
H.J. Netter ◽  
V. Bichko ◽  
D. Lazinski ◽  
J. Taylor
Keyword(s):  
Rna Editing ◽  
Hepatitis Delta Virus ◽  
Replication Cycle ◽  
Hepatitis Delta ◽  
Human Hepatitis ◽  
Delta Virus

scholarly journals Erratum: RNA editing of hepatitis delta virus antigenome by dsRNA-adenosine deaminase

Nature ◽  
1996 ◽  
Vol 381 (6580) ◽  
pp. 346-346 ◽  
Author(s):  
Andrew G. Polson ◽  
Brenda L. Bass ◽  
John L. Casey
Keyword(s):  
Adenosine Deaminase ◽  
Rna Editing ◽  
Hepatitis Delta Virus ◽  
Hepatitis Delta ◽  
Delta Virus

scholarly journals Hepatitis Delta Virus RNA Encoding the Large Delta Antigen Cannot Sustain Replication due to Rapid Accumulation of Mutations Associated with RNA Editing

2003 ◽  
Vol 77 (22) ◽  
pp. 12048-12056 ◽  
Author(s):  
Thomas B. Macnaughton ◽  
Yi-Ija Li ◽  
Alison L. Doughty ◽  
Michael M. C. Lai
Keyword(s):  
Rna Editing ◽  
Hepatitis Delta Virus ◽  
Rna Replication ◽  
Site Directed Mutagenesis ◽  
Editing Event ◽  
Putative Promoter Region ◽  
Hepatitis Delta ◽  
Time Points ◽  
Rna Transfection ◽  
Delta Virus

ABSTRACT Hepatitis delta virus (HDV) contains two RNA species (HDV-S and HDV-L), which encode the small and large forms of hepatitis delta antigens (S- and L-HDAg), respectively. HDV-L RNA is a result of an RNA editing event occurring at an amber/W site of HDV-S RNA. RNA editing must be regulated to prevent premature and excessive accumulation of HDV-L RNA in the viral life cycle. In this study, we used an RNA transfection procedure to study the replication abilities of HDV-L and HDV-S RNA. While HDV-S led to robust RNA replication, HDV-L could not replicate even after 6 days following transfection. The failure of HDV-L to replicate was not due to insufficient amounts of S-HDAg, as identical results were obtained in a cell line that stably overexpresses S-HDAg. Also, it was not due to possible inhibition by L-HDAg, as HDV-S RNA replication was not affected when both HDV-L and HDV-S RNA were cotransfected. Further, when L-HDAg expression from HDV-L RNA was abolished by site-directed mutagenesis, the mutant HDV-L RNA also failed to replicate. Unexpectedly, when the kinetics of RNA replication was examined daily, HDV-L was found to replicate at a low level at the early time points (1 to 2 days posttransfection) but then lose this capability at later time points. Sequence analysis of the replicated HDV-L RNA at day 1 posttransfection showed that it had undergone multiple nucleotide changes, particularly in the region near the putative promoter region of HDV RNA replication. In contrast, very few mutations were found in HDV-S RNA. These results suggest that the editing at the amber/W site triggers a series of additional mutations which rapidly reduce the replication efficiency of the resultant HDV genome and thus help regulate the amount of HDV-L RNA in infected cells. They also explain why L-HDAg is not produced early in HDV infection, despite the fact that HDV-L RNA is present in the virion.

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