RNA Editing and its Control in Hepatitis Delta Virus Replication

Chen, Renxiang; Linnstaedt, Sarah D.; Casey, John L.

doi:10.3390/v2010131

Cited by 11 publications

(7 citation statements)

References 49 publications

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“…The higher efficiency observed in Fig. 1B compared to the previous study is likely due to sequence changes, including editing at the amber/W site (28) in the serum-derived RNA that could decrease the efficiency of replication (17), although the choice of ends for the linear RNA could also contribute (27). Regardless, the in vitro-synthesized circular RNA provides a highly effective method for initiating replication using small amounts of RNA with homogeneous sequence and does not require template switching (22,23) events to initiate replication.…”

Section: Efficient Initiation Of Hdv Replication In Cultured Cells Bycontrasting

confidence: 62%

Hepatitis Delta Antigen Regulates mRNA and Antigenome RNA Levels during Hepatitis Delta Virus Replication

Harichandran

Shen

Tsoris

et al. 2019

J Virol

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Hepatitis delta virus (HDV) is a satellite of hepatitis B virus that increases the severity of acute and chronic liver disease. HDV produces three processed RNAs that accumulate in infected cells: the circular genome; the circular antigenome, which serves as a replication intermediate; and lesser amounts of the mRNA, which encodes the sole viral protein, hepatitis delta antigen (HDAg). The HDV genome and antigenome RNAs form ribonucleoprotein complexes with HDAg. Although HDAg is required for HDV replication, it is not known how the relative amounts of HDAg and HDV RNA affect replication, or whether HDAg synthesis is regulated by the virus. Using a novel transfection system in which HDV replication is initiated using in vitro-synthesized circular HDV RNAs, HDV replication was found to depend strongly on the relative amounts of HDV RNA and HDAg. HDV controls these relative amounts via differential effects of HDAg on the production of HDV mRNA and antigenome RNA, both of which are synthesized from the genome RNA template. mRNA synthesis is favored at low HDAg levels but becomes saturated at high HDAg concentrations. Antigenome RNA accumulation increases linearly with HDAg and dominates at high HDAg levels. These results provide a conceptual model for how HDV antigenome RNA production and mRNA transcription are controlled from the earliest stage of infection onward and also demonstrate that, in this control, HDV behaves similarly to other negative-strand RNA viruses, even though there is no genetic similarity between them. IMPORTANCE Hepatitis delta virus (HDV) is a satellite of hepatitis B virus that increases the severity of liver disease; approximately 15 million people are chronically infected worldwide. There are no licensed therapies available. HDV is not related to any known virus, and few details regarding its replication cycle are known. One key question is whether and how HDV regulates the relative amounts of viral RNA and protein in infected cells. Such regulation might be important because the HDV RNA and protein form complexes that are essential for HDV replication, and the proper stoichiometry of these complexes could be critical for their function. Our results show that the relative amounts of HDV RNA and protein in cells are indeed important for HDV replication and that the virus does control them. These observations indicate that further study of these regulatory mechanisms is required to better understand replication of this serious human pathogen.

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Section: Efficient Initiation Of Hdv Replication In Cultured Cells Bycontrasting

confidence: 62%

Hepatitis Delta Antigen Regulates mRNA and Antigenome RNA Levels during Hepatitis Delta Virus Replication

Harichandran

Shen

Tsoris

et al. 2019

J Virol

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“…R1, R2 = ribozyme domain; C = C-terminal amino acid extension; A = PolyA. HDAg: hepatitis delta antigen; E = RNA editing site (position at nt 1015) [ 38 ]. Numbering is according to HDV strain NC1001653.…”

Section: Resultsmentioning

confidence: 99%

Prevalence and genotype distribution of hepatitis delta virus among chronic hepatitis B carriers in Central Vietnam

Nguyen

Trung

et al. 2017

PLoS ONE

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Hepatitis D virus (HDV) infection plays an important role in liver diseases. However, the molecular epidemiology and impact of HDV infection in chronic hepatitis B (CHB) remain uncertain in Vietnam. This cross-sectional study aimed to investigate the prevalence and genotype distribution of HDV among HBsAg-positive patients in Central Vietnam. 250 CHB patients were tested for HDV using newly established HDV-specific RT-PCR techniques. HDV genotypes were determined by direct sequencing. Of the 250 patients 25 (10%) had detectable copies of HDV viral RNA. HDV-2 was predominant (20/25; 80%) followed by HDV-1 (5/25; 20%). Proven HDV genotypes share the Asian nomenclature. Chronic hepatitis B patients with concomitant HDV-1 showed higher HBV loads as compared to HDV-2 infected patients [median log10 (HBV-DNA copies/ml): 8.5 vs. 4.4, P = 0.036]. Our findings indicate that HDV infection is highly prevalent and HDV-2 is predominant in Central Vietnam. The data will add new information to the management of HBsAg-positive patients in a highly HBV endemic region to in- or exclude HDV infection in terms of diagnostic and treatment options.

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“…HDAg is expressed in two isoforms, small (SHDAg) and large (L-HDAg). S-HDAg is required for the replication of HDV, while L-HDAg inhibits viral replication and is required for the envelopment of the HDV genomic RNA by hepatitis B virus proteins [123] . Bell et al [124] found that over half of the L-HDAg domains were localized beside ND10.…”

Section: Rna Virusesmentioning

confidence: 99%

Nuclear domain 10 of the viral aspect

Rivera-Molina

Martínez²,

Tang³

2013

WJV

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Nuclear domain 10 (ND10) are spherical bodies distributed throughout the nucleoplasm and measuring around 0.2-1.0 μm. First observed under an electron microscope, they were originally described as dense bodies found in the nucleus. They are known by a number of other names, including Promyelocytic Leukemia bodies (PML bodies), Kremer bodies, and PML oncogenic domains. ND10 are frequently associated with Cajal bodies and cleavage bodies. It has been suggested that they play a role in regulating gene transcription. ND10 were originally characterized using human autoantisera, which recognizes Speckled Protein of 100 kDa, from patients with primary biliary cirrhosis. At the immunohistochemical level, ND10 appear as nuclear punctate structures, with 10 indicating the approximate number of dots per nucleus observed. ND10 do not colocalize with kinetochores, centromeres, sites of mRNA processing, or chromosomes. Resistance of ND10 antigens to nuclease digestion and salt extraction suggest that ND10 are associated with the nuclear matrix.They are often identified by immunofluorescent assay using specific antibodies against PML, Death domainassociated protein, nuclear dot protein (NDP55), and so on. The role of ND10 has long been the subject of investigation, with the specific connection of ND10 and viral infection having been a particular focus for almost 20 years. This review summarizes the relationship of ND10 and viral infection. Some future study directions are also discussed.

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RNA Editing and its Control in Hepatitis Delta Virus Replication

Cited by 11 publications

References 49 publications

Hepatitis Delta Antigen Regulates mRNA and Antigenome RNA Levels during Hepatitis Delta Virus Replication

Hepatitis Delta Antigen Regulates mRNA and Antigenome RNA Levels during Hepatitis Delta Virus Replication

Prevalence and genotype distribution of hepatitis delta virus among chronic hepatitis B carriers in Central Vietnam

Nuclear domain 10 of the viral aspect

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