Hepatitis Delta Virus RNA Replication

Tseng, Chung-Hsin; Lai, Michael M. C.

doi:10.3390/v1030818

Cited by 62 publications

(76 citation statements)

References 74 publications

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“…8 Notably, there is also a general consensus involving Pol II in replication of HDV but, while some studies implicate this enzyme in the nucleoplasmic synthesis of genomic and antigenomic strands (in addition to the subgenomic mRNA of antigenomic sense encoding ∂Ag), others indicate that elongation of antigenomic strands is catalyzed by Pol I in the nucleolus; to complicate even more the situation, new data have additionally implicated Pol III. Evidence supporting these partially contradictory views, as well as the experimental approaches on which they are based, can be found in the original publications and in recent reviews in reference [41][42][43]. Crystallographic analysis has shown that an RNA templateproduct duplex occupies in Pol II the same site as the DNA-RNA was coined, while the linear form is predominantly encapsidated in viroid-like satellite RNAs of nepo-and luteoviruses.…”

Section: Polymerization Of Rna Strandsmentioning

confidence: 94%

“…A final related issue, still controversial, is whether synthesis of the subgenomic ∂Ag-mRNA is linked to the HDV replication, or the processes are independent and reside in distinct complexes. 42 This complication does not exist in viroids and viroid-like satellite RNAs, which do not encode any protein in their genomes and, therefore, there is no possible interference between replication and transcription.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

“…Moreover, S-∂Ag is essential for accumulation (and perhaps replication) of HDV RNA, 45 and can be regulated by different post-transcriptional modifications as also can be L-∂Ag, 46 which has a dominant negative effect on viral RNA accumulation. 41,42 RNA elongation in the family Avsunviroidae appears to be catalyzed by a nuclear-encoded RNA polymerase (NEP) that is translocated into plastids, rather than by a plastid-encoded polymerase (PEP). Data supporting this notion include the effects of tagetitoxin, which inhibits PEP but not NEP, on in vitro synthesis of host and viroid RNAs by chloroplastic preparations from ASBVd-infected tissue, 47 together with active PLMVd replication in peach leaves showing a PLMVd-induced albinism wherein PEP-dependent transcription is essentially abolished.…”

Section: Cleavage or Self-cleavage Of Concatemeric Rna Intermediatesmentioning

confidence: 99%

See 2 more Smart Citations

Rolling-circle replication of viroids, viroid-like satellite RNAs and hepatitis delta virus: Variations on a theme

Flores¹,

Grubb²,

Elleuch³

et al. 2011

RNA Biology

113

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Section: Polymerization Of Rna Strandsmentioning

confidence: 94%

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

Section: Cleavage or Self-cleavage Of Concatemeric Rna Intermediatesmentioning

confidence: 99%

See 1 more Smart Citation

Rolling-circle replication of viroids, viroid-like satellite RNAs and hepatitis delta virus: Variations on a theme

Flores¹,

Grubb²,

Elleuch³

et al. 2011

RNA Biology

113

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“…Thus, this protein aids transcription of both DNA and RNA templates by a DdRP, though the mechanism by which it accomplishes a switch in substrate specificity remains unclear. HDV encodes two proteins, small and large delta antigens (HDAg-S and HDAg-L) that are involved in HDV transcription/replication and packaging, respectively (Tseng and Lai, 2009). HDAg-L is encoded by a read-through of mRNA encoding the HDAg-S, thereby differing from the latter by having 19 extra amino acids in the C terminus.…”

Section: Discussionmentioning

confidence: 99%

A Land Plant-Specific Transcription Factor Directly Enhances Transcription of a Pathogenic Noncoding RNA Template by DNA-Dependent RNA Polymerase II

Wang

et al. 2015

The Plant Cell

106

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Some DNA-dependent RNA polymerases (DdRPs) possess RNA-dependent RNA polymerase activity, as was first discovered in the replication of Potato spindle tuber viroid (PSTVd) RNA genome in tomato (Solanum lycopersicum). Recent studies revealed that this activity in bacteria and mammals is important for transcriptional and posttranscriptional regulatory mechanisms. Here, we used PSTVd as a model to uncover auxiliary factors essential for RNA-templated transcription by DdRP. PSTVd replication in the nucleoplasm generates (2)-PSTVd intermediates and (+)-PSTVd copies. We found that the Nicotiana benthamiana canonical 9-zinc finger (ZF) Transcription Factor IIIA (TFIIIA-9ZF) as well as its variant TFIIIA-7ZF interacted with (+)-PSTVd, but only TFIIIA-7ZF interacted with (2)-PSTVd. Suppression of TFIIIA-7ZF reduced PSTVd replication, and overexpression of TFIIIA-7ZF enhanced PSTVd replication in planta. Consistent with the locale of PSTVd replication, TFIIIA-7ZF was found in the nucleoplasm and nucleolus, in contrast to the strictly nucleolar localization of TFIIIA-9ZF. Footprinting assays revealed that only TFIIIA-7ZF bound to a region of PSTVd critical for initiating transcription. Furthermore, TFIIIA-7ZF strongly enhanced the in vitro transcription of circular (+)-PSTVd by partially purified Pol II. Together, our results identify TFIIIA-7ZF as a dedicated cellular transcription factor that acts in DdRP-catalyzed RNA-templated transcription, highlighting both the extraordinary evolutionary adaptation of viroids and the potential of DdRPs for a broader role in cellular processes.

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“…The circular HDV RNA genome is the smallest known to infect humans and is replicated by host RNA polymerase (8). Replication occurs through a double-rolling-circle mechanism that involves the circular reverse complement of the genome, the antigenome (9,10). For both of these circular RNAs, one-half exhibits substantial sequence complementarity to the other half, such that they collapse into linear closed hairpin structures in which short (2 to 10 nucleotides [nt]) base-paired segments are interspersed with small bulges and internal loops but no branches (11,12).…”

mentioning

confidence: 99%

Hepatitis Delta Antigen Requires a Flexible Quasi-Double-Stranded RNA Structure To Bind and Condense Hepatitis Delta Virus RNA in a Ribonucleoprotein Complex

Griffin

Chasovskikh

Dritschilo

et al. 2014

J Virol

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The circular genome and antigenome RNAs of hepatitis delta virus (HDV) form characteristic unbranched, quasi-doublestranded RNA secondary structures in which short double-stranded helical segments are interspersed with internal loops and bulges. The ribonucleoprotein complexes (RNPs) formed by these RNAs with the virus-encoded protein hepatitis delta antigen (HDAg) perform essential roles in the viral life cycle, including viral replication and virion formation. Little is understood about the formation and structure of these complexes and how they function in these key processes. Here, the specific RNA features required for HDAg binding and the topology of the complexes formed were investigated. Selective 2=OH acylation analyzed by primer extension (SHAPE) applied to free and HDAg-bound HDV RNAs indicated that the characteristic secondary structure of the RNA is preserved when bound to HDAg. Notably, the analysis indicated that predicted unpaired positions in the RNA remained dynamic in the RNP. Analysis of the in vitro binding activity of RNAs in which internal loops and bulges were mutated and of synthetically designed RNAs demonstrated that the distinctive secondary structure, not the primary RNA sequence, is the major determinant of HDAg RNA binding specificity. Atomic force microscopy analysis of RNPs formed in vitro revealed complexes in which the HDV RNA is substantially condensed by bending or wrapping. Our results support a model in which the internal loops and bulges in HDV RNA contribute flexibility to the quasi-double-stranded structure that allows RNA bending and condensing by HDAg. IMPORTANCE RNA-protein complexes (RNPs) formed by the hepatitis delta virus RNAs and protein, HDAg, perform critical roles in virus replication.Neither the structures of these RNPs nor the RNA features required to form them have been characterized. HDV RNA is unusual in that it forms an unbranched quasi-double-stranded structure in which short base-paired segments are interspersed with internal loops and bulges. We analyzed the role of the HDV RNA sequence and secondary structure in the formation of a minimal RNP and visualized the structure of this RNP using atomic force microscopy. Our results indicate that HDAg does not recognize the primary sequence of the RNA; rather, the principle contribution of unpaired bases in HDV RNA to HDAg binding is to allow flexibility in the unbranched quasi-double-stranded RNA structure. Visualization of RNPs by atomic force microscopy indicated that the RNA is significantly bent or condensed in the complex.

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Hepatitis Delta Virus RNA Replication

Cited by 62 publications

References 74 publications

Rolling-circle replication of viroids, viroid-like satellite RNAs and hepatitis delta virus: Variations on a theme

Rolling-circle replication of viroids, viroid-like satellite RNAs and hepatitis delta virus: Variations on a theme

A Land Plant-Specific Transcription Factor Directly Enhances Transcription of a Pathogenic Noncoding RNA Template by DNA-Dependent RNA Polymerase II

Hepatitis Delta Antigen Requires a Flexible Quasi-Double-Stranded RNA Structure To Bind and Condense Hepatitis Delta Virus RNA in a Ribonucleoprotein Complex

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