The Delta Agent

Rizzetto, M.

doi:10.1002/hep.1840030518

Cited by 375 publications

(42 citation statements)

References 31 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Hepatitis delta virus (HDV) increases the severity of liver disease in patients simultaneously infected with its helper, Hepatitis B Virus (HBV) (Rizzetto 1983). The ca.…”

Section: Introductionmentioning

confidence: 99%

The role of a metastable RNA secondary structure in hepatitis delta virus genotype III RNA editing

Linnstaedt

Kasprzak²,

Shapiro

et al. 2006

RNA

View full text Add to dashboard Cite

RNA editing plays a critical role in the life cycle of hepatitis delta virus (HDV). The host editing enzyme ADAR1 recognizes specific RNA secondary structure features around the amber/W site in the HDV antigenome and deaminates the amber/W adenosine. A previous report suggested that a branched secondary structure is necessary for editing in HDV genotype III. This branched structure, which is distinct from the characteristic unbranched rod structure required for HDV replication, was only partially characterized, and knowledge concerning its formation and stability was limited. Here, we examine the secondary structures, conformational dynamics, and amber/W site editing of HDV genotype III RNA using a miniaturized HDV genotype III RNA in vitro. Computational analysis of this RNA using the MPGAfold algorithm indicated that the RNA has a tendency to form both metastable and stable unbranched secondary structures. Moreover, native polyacrylamide gel electrophoresis demonstrated that this RNA forms both branched and unbranched rod structures when transcribed in vitro. As predicted, the branched structure is a metastable structure that converts readily to the unbranched rod structure. Only branched RNA was edited at the amber/W site by ADAR1 in vitro. The structural heterogeneity of HDV genotype III RNA is significant because not only are both conformations of the RNA functionally important for viral replication, but the ratio of the two forms could modulate editing by determining the amount of substrate RNA available for modification.

show abstract

“…Hepatitis delta virus (HDV) increases the severity of liver disease in patients simultaneously infected with its helper, Hepatitis B Virus (HBV) (Rizzetto 1983). The ca.…”

Section: Introductionmentioning

confidence: 99%

The role of a metastable RNA secondary structure in hepatitis delta virus genotype III RNA editing

Linnstaedt

Kasprzak²,

Shapiro

et al. 2006

RNA

View full text Add to dashboard Cite

show abstract

“…The hepatitis delta virus (HDV) is a defective RNA virus which requires the hepatitis B virus (HBV) surface antigen (HBsAg) for complete replication and transmission, although the full extent of the HBV helper function has not been unexplored (27,34). The HDV genome is a small, 1,678-nucleotide single-stranded RNA with a circular configuration that can form a rod-like structure with at least 70% paired bases (16,35).…”

mentioning

confidence: 99%

Establishment of a Novel Quantitative Hepatitis D Virus (HDV) RNA Assay Using the Cobas TaqMan Platform To Study HDV RNA Kinetics

et al. 2010

View full text Add to dashboard Cite

Determination of hepatitis D virus (HDV) viremia represents the "gold standard" for the diagnosis of HDV infection. Hepatitis B virus (HBV)-HDV coinfection frequently leads to end-stage liver disease and hepatocellular carcinoma.No commercial assay for HDV RNA quantification that includes automated nucleic acid extraction is available, and in-house PCR tests are not well standardized. However, knowledge of HDV RNA levels may give important information for patient management and could be a useful tool for monitoring the response to antiviral therapies. One platform that is widely used for HBV DNA or HCV RNA quantification is the Cobas Ampliprep/TaqMan system. Using the utility channel of this platform, we established a novel protocol for TaqMan-based HDV RNA quantification after automatic extraction of RNA by the Ampliprep system. The assay was specific and showed linearity over a wide range from 3 ؋ 10 2 to 10 7 copies/ml. Reproducibility was demonstrated by determination of the interrun and intrarun variabilities, which were similar to those achieved with the commercially available Cobas TaqMan assays for HCV RNA and HBV DNA. HDV RNA levels were stable in whole blood (n ‫؍‬ 4), plasma (n ‫؍‬ 3), and serum (n ‫؍‬ 3) samples at room temperature for up to 6 days. Importantly, HDV RNA viremia showed only minor fluctuations, with the log 10 coefficient of variation being between 1.3 and 11.2% for hepatitis delta patients studied every 2 weeks for up to 3 months (n ‫؍‬ 6), while a rapid viral decline was observed early during treatment with pegylated alfa-2a interferon (n ‫؍‬ 6). In conclusion, this novel automated HDV RNA assay is a useful tool for monitoring HDV-infected patients both before and during antiviral therapy.Hepatitis delta is the most severe form of chronic viral hepatitis in humans. The hepatitis delta virus (HDV) is a defective RNA virus which requires the hepatitis B virus (HBV) surface antigen (HBsAg) for complete replication and transmission, although the full extent of the HBV helper function has not been unexplored (27,34). The HDV genome is a small, 1,678-nucleotide single-stranded RNA with a circular configuration that can form a rod-like structure with at least 70% paired bases (16, 35). The HDV RNA encodes small and large hepatitis delta antigens as the sole proteins (34).Hepatitis delta occurs only in HBsAg-positive individuals either as an acute coinfection or as a superinfection in patients with chronic hepatitis B (9). Several studies have shown that chronic HDV infection leads to more severe liver disease than chronic HBV monoinfection, with the course of progression of the fibrosis being accelerated, the risk of hepatocellular carcinoma being increased, and early decompensation occurring in the setting of established cirrhosis (9,12,13,36). Simultaneous HBV and HDV infection has also been shown to be more severe than infection with HBV alone in chimpanzees (6).The current treatment options for patients with delta hepatitis are very limited, as alfa interferon is able to clear HDV only ...

show abstract

“…Human hepatitis delta virus (HDV) is an unusual subviral agent that increases the severity of acute and chronic liver disease in those infected with its helper, hepatitis B virus (23). The HDV genome is a 1,680-nucleotide (nt) single-stranded circular RNA that is replicated by a double-rolling-circle mechanism (reviewed in references 15 and 28).…”

mentioning

confidence: 99%

Multimerization of Hepatitis Delta Antigen Is a Critical Determinant of RNA Binding Specificity

Lin

Defenbaugh

Casey

2010

J Virol

View full text Add to dashboard Cite

Hepatitis delta virus (HDV) RNA forms an unbranched rod structure that is associated with hepatitis delta antigen (HDAg) in cells replicating HDV. Previous in vitro binding experiments using bacterially expressed HDAg showed that the formation of a minimal ribonucleoprotein complex requires an HDV unbranched rod RNA of at least about 300 nucleotides (nt) and suggested that HDAg binds the RNA as a multimer of fixed size. The present study specifically examines the role of HDAg multimerization in the formation of the HDV ribonucleoprotein complex (RNP). Disruption of HDAg multimerization by site-directed mutagenesis was found to profoundly alter the nature of RNP formation. Mutant HDAg proteins defective for multimerization exhibited neither the 300-nt RNA size requirement for binding nor specificity for the unbranched rod structure. The results unambiguously demonstrate that HDAg binds HDV RNA as a multimer and that the HDAg multimer is formed prior to binding the RNA. RNP formation was found to be temperature dependent, which is consistent with conformational changes occurring on binding. Finally, analysis of RNPs constructed with unbranched rod RNAs successively longer than the minimum length indicated that multimeric binding is not limited to the first HDAg bound and that a minimum RNA length of between 604 and 714 nt is required for binding of a second multimer. The results confirm the previous proposal that HDAg binds as a large multimer and demonstrate that the multimer is a critical determinant of the structure of the HDV RNP. Human hepatitis delta virus (HDV) is an unusual subviral agent that increases the severity of acute and chronic liver disease in those infected with its helper, hepatitis B virus (23).The HDV genome is a 1,680-nucleotide (nt) single-stranded circular RNA that is replicated by a double-rolling-circle mechanism (reviewed in references 15 and 28). Both the genome and antigenome RNAs form a characteristic unbranched rod structure due to 70% sequence complementarity between the noncoding and coding regions of the RNA (10, 11, 31). HDV encodes just one protein, hepatitis delta antigen (HDAg), which forms ribonucleoprotein (RNP) complexes with both the genome and the antigenome in cells replicating HDV (3,5,30). These complexes play fundamental roles in viral RNA replication and packaging and their characterization is essential for understanding these processes, which are not well characterized.HDAg has been shown to form dimers and higher order multimers, even in the absence of HDV RNA (25,30,32). The multimerization activity has been localized to the amino-terminal third of the 195-amino-acid (aa) protein (12,24,30,32). X-ray crystallographic analysis of a peptide comprised of aa 12 to 60 indicated that antiparallel dimers are stabilized by a coiled coil (aa 16 to 48), as well as a hydrophobic core region (aa 50 to 60) that also stabilizes interactions between dimers such that an octameric structure may form (35). Zuccola et al. found that bacterially expressed HDAg could be cross-linked ...

show abstract

The Delta Agent

Cited by 375 publications

References 31 publications

The role of a metastable RNA secondary structure in hepatitis delta virus genotype III RNA editing

The role of a metastable RNA secondary structure in hepatitis delta virus genotype III RNA editing

Establishment of a Novel Quantitative Hepatitis D Virus (HDV) RNA Assay Using the Cobas TaqMan Platform To Study HDV RNA Kinetics

Multimerization of Hepatitis Delta Antigen Is a Critical Determinant of RNA Binding Specificity

Contact Info

Product

Resources

About