A Mathematical Analysis of HDV Genotypes: From Molecules to Cells

Hepatitis D virus (HDV) is classified according to eight genotypes. The various genotypes are included in the HDVdb database, where each HDV sequence is specified by its genotype. In this contribution, a mathematical analysis is performed on RNA sequences in HDVdb. The RNA folding predicted structures of the Genbank HDV genome sequences in HDVdb are classified according to their coarse-grain tree-graph representation. The analysis allows discarding in a simple and efficient way the vast majority of the sequences that exhibit a rod-like structure, which is important for the virus replication, to attempt to discover other biological functions by structure consideration. After the filtering, there remain only a small number of sequences that can be checked for their additional stem-loops besides the main one that is known to be responsible for virus replication. It is found that a few sequences contain an additional stem-loop that is responsible for RNA editing or other possible functions. These few sequences are grouped into two main classes, one that is well-known experimentally belonging to genotype 3 for patients from South America associated with RNA editing, and the other that is not known at present belonging to genotype 7 for patients from Cameroon. The possibility that another function besides virus replication reminiscent of the editing mechanism in HDV genotype 3 exists in HDV genotype 7 has not been explored before and is predicted by eigenvalue analysis. Finally, when comparing native and shuffled sequences, it is shown that HDV sequences belonging to all genotypes are accentuated in their mutational robustness and thermodynamic stability as compared to other viruses that were subjected to such an analysis.

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A Mathematical Analysis of RNA Structural Motifs in Viruses

Mathematics ◽

10.3390/math9060585 ◽

2021 ◽

Vol 9 (6) ◽

pp. 585

Author(s):

Alexander Churkin ◽

Franziska Totzeck ◽

Rami Zakh ◽

Marina Parr ◽

Tamir Tuller ◽

...

Keyword(s):

Mathematical Analysis ◽

Rna Structure ◽

Viral Rna ◽

Graph Representation ◽

Folding Energy ◽

Mutational Robustness ◽

Large Dataset ◽

Structural Motifs ◽

Stem Loop ◽

Rna Structural Motifs

RNA stem-loop structures play an important role in almost every step of the viral replication cycle. In this contribution, a mathematical analysis is performed on a large dataset of RNA secondary structure elements in the coding regions of viruses by using topological indices that capture the Laplacian eigenvalues of the associated RNA graph representations and thereby enable structural classification, supplemented by folding energy and mutational robustness. The application of such an analysis for viral RNA structural motifs is described, being able to extract structural categories such as stem-loop structures of different sizes according to the tree-graph representation of the RNA structure, in our attempt to find novel functional motifs. While the analysis is carried on a large dataset of viral RNA structures, it can be applied more generally to other data that involve RNA secondary structures in biological agents.

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Hepatitis D Virus Replication

Cold Spring Harbor Perspectives in Medicine ◽

10.1101/cshperspect.a021568 ◽

2015 ◽

Vol 5 (11) ◽

pp. a021568 ◽

Cited By ~ 20

Author(s):

John M. Taylor

Keyword(s):

Virus Replication ◽

Hepatitis D ◽

Hepatitis D Virus

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PRESa2i: incremental decision trees for prediction of Adenosine to Inosine RNA editing sites

F1000Research ◽

10.12688/f1000research.22823.1 ◽

2020 ◽

Vol 9 ◽

pp. 262

Author(s):

Alif Choyon ◽

Ashiqur Rahman ◽

Md. Hasanuzzaman ◽

Dewan Md Farid ◽

Swakkhar Shatabda

Keyword(s):

Rna Editing ◽

Web Application ◽

State Of The Art ◽

Independent Set ◽

Prediction Tool ◽

Decision Tree Algorithm ◽

Rna Sequences ◽

Feature Selection Technique ◽

Selection Technique ◽

Protein Encoding

RNA editing is a very crucial cellular process affecting protein encoding and is sometimes correlated with the cause of fatal diseases, such as cancer. Thus knowledge about RNA editing sites in a RNA sequence is very important. Adenosine to Inosine (A-to-I) is the most common of the RNA editing events. In this paper,we present PRESa2i, a computation prediction tool for identification of A-to-I RNA editing sites in given RNA sequences. PRESa2i uses a simple, yet effective set of sequence based features generated from RNA sequences and a novel feature selection technique. It uses an incremental decision tree algorithm as the classification algorithm. On a standard benchmark dataset and independent set, it achieves 86.48% accuracy and 90.67% sensitivity and significantly outperforms state-of-the-art methods. We have also implemented a web application based on PRESa2i and made it available freely at: http://brl.uiu.ac.bd/presa2i/index.php. The materials for this paper are also available to use from: https://github.com/swakkhar/RNA-Editing/.

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Clinical outcomes in patients with hepatitis D, cirrhosis and persistent hepatitis B virus replication, and receiving long-term tenofovir or entecavir

Alimentary Pharmacology & Therapeutics ◽

10.1111/apt.15188 ◽

2019 ◽

Vol 49 (8) ◽

pp. 1071-1076 ◽

Cited By ~ 11

Author(s):

Giuseppina Brancaccio ◽

Massimo Fasano ◽

Adriano Grossi ◽

Teresa Antonia Santantonio ◽

Giovanni B. Gaeta

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Clinical Outcomes ◽

Virus Replication ◽

Hepatitis D ◽

B Virus

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Discovering common stem-loop motifs in unaligned RNA sequences

Nucleic Acids Research ◽

10.1093/nar/29.10.2135 ◽

2001 ◽

Vol 29 (10) ◽

pp. 2135-2144 ◽

Cited By ~ 77

Author(s):

J. Gorodkin

Keyword(s):

Rna Sequences ◽

Stem Loop

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HBV/HDV co-infection in the Western Brazilian Amazonia: an intriguing mutation among HDV genotype 3 carriers

Journal of Viral Hepatitis ◽

10.1111/jvh.12267 ◽

2014 ◽

Vol 21 (12) ◽

pp. 921-924 ◽

Cited By ~ 10

Author(s):

A. Kay ◽

E. Melo da Silva ◽

H. Pedreira ◽

S. Negreiros ◽

C. Lobato ◽

...

Keyword(s):

Genotype 3 ◽

Brazilian Amazonia ◽

Hdv Genotype

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Varied assembly and RNA editing efficiencies between genotypes I and II hepatitis D virus and their implications

Journal of Hepatology ◽

10.1016/s0168-8278(02)80627-4 ◽

2002 ◽

Vol 36 ◽

pp. 177

Author(s):

Sheng-Chieh Hsu ◽

Wan-Jr Syu ◽

I-Jane Sheen ◽

Hui-Ting Liu ◽

King-Song Jeng ◽

...

Keyword(s):

Rna Editing ◽

Hepatitis D ◽

Hepatitis D Virus

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A plant mitochondrial sequence transcribed in transgenic tobacco chloroplasts is not edited.

Molecular and Cellular Biology ◽

10.1128/mcb.15.3.1377 ◽

1995 ◽

Vol 15 (3) ◽

pp. 1377-1381 ◽

Cited By ~ 27

Author(s):

C A Sutton ◽

O V Zoubenko ◽

M R Hanson ◽

P Maliga

Keyword(s):

Transgenic Tobacco ◽

Rna Editing ◽

Ribosomal Protein Gene ◽

Regulatory Sequences ◽

Mitochondrial Rna ◽

Higher Plant ◽

Rna Sequences ◽

Exon 2 ◽

Chimeric Genes ◽

Gene Regulatory

RNA editing occurs in two higher-plant organelles, chloroplasts and mitochondria. Because chloroplasts and mitochondria exhibit some similarity in editing site selection, we investigated whether mitochondrial RNA sequences could be edited in chloroplasts. We produced transgenic tobacco plants that contained chimeric genes in which the second exon of a Petunia hybrida mitochondrial coxII gene was under the control of chloroplast gene regulatory sequences. coxII transcripts accumulated to low or high levels in transgenic chloroplasts containing chimeric genes with the plastid ribosomal protein gene rps16 or the rRNA operon promoter, respectively. Exon 2 of coxII was chosen because it carries seven editing sites and is edited in petunia mitochondria even when located in an abnormal context in an aberrant recombined gene. When editing of the coxII transcripts in transgenic chloroplasts was examined, no RNA editing at any of the usual sites was detected, nor was there any novel editing at any other sites. These results indicate that the RNA editing mechanisms of chloroplasts and mitochondria are not identical but must have at least some organelle-specific components.

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Demonstration of Nicking/Joining Activity at the Origin of DNA Replication Associated with the Rep and Rep′ Proteins of Porcine Circovirus Type 1

Journal of Virology ◽

10.1128/jvi.02506-05 ◽

2006 ◽

Vol 80 (13) ◽

pp. 6225-6234 ◽

Cited By ~ 44

Author(s):

Tobias Steinfeldt ◽

Tim Finsterbusch ◽

Annette Mankertz

Keyword(s):

Dna Replication ◽

Virus Replication ◽

Porcine Circovirus Type ◽

Porcine Circovirus ◽

Loop Structure ◽

Stem Loop ◽

Single Strand Break ◽

Stem Loop Structure ◽

Rep Proteins

ABSTRACT The replication of porcine circovirus type 1 (PCV1) is thought to occur by rolling-circle replication (RCR), whereby the introduction of a single-strand break generates a free 3′-hydroxyl group serving as a primer for subsequent DNA synthesis. The covalently closed, single-stranded genome of PCV1 replicates via a double-stranded replicative intermediate, and the two virus-encoded replication-associated proteins Rep and Rep′ have been demonstrated to be necessary for virus replication. However, although postulated to be involved in RCR-based virus replication, the mechanism of action of Rep and Rep′ is as yet unknown. In this study, the ability of PCV1 Rep and Rep′ to “nick” and “join” strand discontinuities within synthetic oligonucleotides corresponding to the origin of replication of PCV1 was investigated in vitro. Both proteins were demonstrated to be able to cleave the viral strand between nucleotides 7 and 8 within the conserved nonanucleotide motif (5′-TAGTATTAC-3′) located at the apex of a putative stem-loop structure. In addition, the Rep and Rep′ proteins of PCV1 were demonstrated to be capable of joining viral single-stranded DNA fragments, suggesting that these proteins also play roles in the termination of virus DNA replication. This joining activity was demonstrated to be strictly dependent on preceding substrate cleavage and the close proximity of origin fragments accomplished by base pairing in the stem-loop structure. The dual “nicking/joining” activities associated with PCV1 Rep and Rep′ are pivotal events underlying the RCR-based replication of porcine circoviruses in mammalian cells.

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