delta Agent: association of delta antigen with hepatitis B surface antigen and RNA in serum of delta-infected chimpanzees.

Rizzetto, Mario; Hoyer, Bill H.; Canese, M. G.; Shih, J. Wai-Kuo; Purcell, Robert H.; Gerin, John L.

doi:10.1073/pnas.77.10.6124

Cited by 403 publications

(287 citation statements)

References 18 publications

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“…15 HDV is not an autonomous virus, as it requires a coinfection by fully functional HBV or other helper 124 Nathan Riccitelli and Andrej Lupták hepadnaviruses. [16][17][18] Individuals infected with both HDV and an associated helper virus experience an increased rate of liver cirrhosis and an increased chance of developing liver cancer in chronic infections. 18 In these instances of coinfection, a decrease in helper virus particles is observed upon detection of HDV markers.…”

Section: Hepatitis Delta Virusmentioning

confidence: 99%

“…18 In these instances of coinfection, a decrease in helper virus particles is observed upon detection of HDV markers. 16 The HDV genome is a single-stranded circular RNA molecule of approximately 1700 nucleotides (nt). 18 Upon infection, the RNA is transcribed by a rolling-circle mechanism using host machinery to produce its antigenomic form that is subject to one of two pathways (Fig.…”

Section: Hepatitis Delta Virusmentioning

confidence: 99%

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HDV Family of Self-Cleaving Ribozymes

Riccitelli¹,

Lupták²

2013

Progress in Molecular Biology and Translational Science

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Section: Hepatitis Delta Virusmentioning

confidence: 99%

Section: Hepatitis Delta Virusmentioning

confidence: 99%

HDV Family of Self-Cleaving Ribozymes

Riccitelli¹,

Lupták²

2013

Progress in Molecular Biology and Translational Science

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“…Hepatitis delta virus (HDV) is a satellite virus and requires the presence of hepatitis B virus (HBV) for virus assembly and production (42). Its genome is a single-stranded, circular RNA of 1.7 kb.…”

mentioning

confidence: 99%

Hepatitis Delta Virus Antigen Is Methylated at Arginine Residues, and Methylation Regulates Subcellular Localization and RNA Replication

Stallcup

Lai³

2004

J Virol

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Hepatitis delta virus (HDV) contains a circular RNA which encodes a single protein, hepatitis delta antigen (HDAg). HDAg exists in two forms, a small form (S-HDAg) and a large form (L-HDAg). S-HDAg can transactivate HDV RNA replication. Recent studies have shown that posttranslational modifications, such as phosphorylation and acetylation, of S-HDAg can modulate HDV RNA replication. Here we show that S-HDAg can be methylated by protein arginine methyltransferase (PRMT1) in vitro and in vivo. The major methylation site is at arginine-13 (R13), which is in the RGGR motif of an RNA-binding domain. The methylation of S-HDAg is essential for HDV RNA replication, especially for replication of the antigenomic RNA strand to form the genomic RNA strand. An R13A mutation in S-HDAg inhibited HDV RNA replication. The presence of a methylation inhibitor, S-adenosyl-homocysteine, also inhibited HDV RNA replication. We further found that the methylation of S-HDAg affected its subcellular localization. Methylation-defective HDAg lost the ability to form a speckled structure in the nucleus and also permeated into the cytoplasm. These results thus revealed a novel posttranslational modification of HDAg and indicated its importance for HDV RNA replication. This and other results further showed that, unlike replication of the HDV genomic RNA strand, replication of the antigenomic RNA strand requires multiple types of posttranslational modification, including the phosphorylation and methylation of HDAg.Hepatitis delta virus (HDV) is a satellite virus and requires the presence of hepatitis B virus (HBV) for virus assembly and production (42). Its genome is a single-stranded, circular RNA of 1.7 kb. Unlike other satellite viruses, HDV can replicate independently of its helper virus, HBV, and does not share sequence homology with HBV. The virus contains a single protein species, hepatitis delta antigen (HDAg), which exists in two forms, including a small form of 195 amino acids (SHDAg) and a large form of 214 amino acids (L-HDAg) (16). HDV RNA replication occurs in the nucleus via host RNA polymerases (11,30,33). The viral genomic RNA replicates by a rolling-circle mechanism into a full-length antigenomic RNA and also transcribes an antigenomic-strand mRNA (0.8 kb) which contains the HDAg open reading frame (ORF). The full-length antigenomic RNA, in turn, is replicated into the genomic-strand RNA by another round of rolling-circle replication. The replication of genomic and antigenomic RNAs and transcription of the HDAg-encoding mRNA are carried out by independent mechanisms, probably by different polymerases (30,31,33). The 0.8-kb mRNA is translated into S-HDAg, which is required for continuous HDV RNA replication (21). In the later stages of viral replication, an RNA editing event occurs at the amber termination codon of the S-HDAg ORF to allow the synthesis of L-HDAg (40, 41), which is required for virus assembly (2, 24). L-HDAg was also thought to inhibit HDV RNA replication when expressed artificially early in viral replication (4...

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“…It requires concurrent infection with hepatitis B, which provides the viral coat protein (1,2). Compared to infection with hepatitis B virus alone, coinfection or superinfection with HDV significantly increases the risk of more severe liver disease, including fulminant hepatitis (3).…”

mentioning

confidence: 99%

Structural requirements for RNA editing in hepatitis delta virus: evidence for a uridine-to-cytidine editing mechanism.

Casey

Bergmann

Brown

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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129

132

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Hepatitis 6 virus (HDV) nucleotide 1012 is edited from uridine to cytidine in 10-40% of the RNA gonomes during replication. This editing event is an important control point in the HDV life cycle because it results in both the packaging of viral RNA and the inhibition of HDV replication. We find that the editing event is highly specific for both the sequences neighboring nucleotide 1012 and the base-paired context of position 1012 within the unbranched rod structure of HDV RNA. Prior studies identified the base transition at nucleotide 1012 but were unable to distinguish between editing of the genomic versus the antigenomic strands [Luo, G. X., Chao, M., Hsieh, S. Y., Sureau, C., Nishikura, K. & Taylor, J. (1990) J. Virol. 64, 1021-1027. In this study, comparisons of mutations that differentiate between base pairing in genomic and antigenomic RNAs indicate that the genomic strand of HDV is the actual editing substrate. We conclude that the virus uses a uridine to cytidine editing mechanism, which is provided by the host cell.Hepatitis 6 virus (HDV) is a subviral pathogen of humans. It requires concurrent infection with hepatitis B, which provides the viral coat protein (1, 2). Compared to infection with hepatitis B virus alone, coinfection or superinfection with HDV significantly increases the risk of more severe liver disease, including fulminant hepatitis (3). The HDV genome is an -1.7-kilobase, single-stranded, circular RNA molecule, which shares some unusual features with plant viroid RNAs (reviewed in ref. 4). The circular RNA molecule possesses significant intramolecular complementarity such that 70%o of the nucleotides can form base pairs in an unbranched rod structure (5, 6). Consistent with a rolling circle replication mechanism similar to that of the plant viroid agents, monomers and multimers of both genomic and antigenomic RNAs are found in infected and transfected cells (7-9). Unlike the viroids, HDV produces a single protein, the hepatitis 8 antigen (HDAg), which is translated from an antigenomic sense mRNA (9, 10). HDAg is an RNA binding protein (11-13) and is found as a mixture of 24-and 27-kDa species in both infected cells and virions (14, 15). The two forms of HDAg play central roles in the HDV replication cycle. p24 is necessary for HDV RNA replication in transfected cells in culture (8), while p27 both inhibits replication (16, 17) and enables packaging of the HDV RNA genome (18). As shown by others (19), the heterogeneity of HDAg likely arises via an RNA editing mechanism wherein the antigenomically encoded stop codon for p24 is changed from UAG to UGG; the resultant translation product, p27, contains an additional 19 amino acids at the C terminus. Because of the circular replication cycle of HDV RNA, the base change was found in both the genomic and antigenomic RNAs (19); it was therefore unclear whether the genomic or the antigenomic RNA is the actual substrate for editing. An A-to-G transition in the antigenomic strand, possibly involving a host doublestranded RNA modifying activi...

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delta Agent: association of delta antigen with hepatitis B surface antigen and RNA in serum of delta-infected chimpanzees.

Cited by 403 publications

References 18 publications

HDV Family of Self-Cleaving Ribozymes

HDV Family of Self-Cleaving Ribozymes

Hepatitis Delta Virus Antigen Is Methylated at Arginine Residues, and Methylation Regulates Subcellular Localization and RNA Replication

Structural requirements for RNA editing in hepatitis delta virus: evidence for a uridine-to-cytidine editing mechanism.

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