Hepatitis Delta Virus histone mimicry drives the recruitment of chromatin remodelers for viral RNA replication

Samarakoon, Natali Abeywickrama; Cortay, Jean‐Claude; Sureau, Camille; Müller, Susanne; Alfaiate, Dulce; Guerrieri, Francesca; Chaikuad, A.; Schröder, Martin; Merle, Philippe; Levrero, Massimo; Dény, Paul

doi:10.1038/s41467-020-14299-9

Cited by 19 publications

(23 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to its high degree of intramolecular base pairing (approximately 74%), the HDV genome folds into rod-like structural elements [ 26 , 27 ] that consist of short dsRNA stems interrupted by single-stranded bulges, as depicted in Figure 1 c. Analyses of 41 HDV isolates indicated that the longest consecutive base-paired regions range from 9 to 15 bp [ 28 ]. At a higher-order level, the HDV genome associates with S-HDAg and forms an RNP, which is proposed to be organized in a nucleosome-like structure during replication [ 29 ]. Antigenome and mRNAs are synthesized using the genome as a template.…”

Section: Hdv Structure Replication and Persistencementioning

confidence: 99%

Interplay between Hepatitis D Virus and the Interferon Response

Zhang

Urban

2020

Viruses

View full text Add to dashboard Cite

Chronic hepatitis D (CHD) is the most severe form of viral hepatitis, with rapid progression of liver-related diseases and high rates of development of hepatocellular carcinoma. The causative agent, hepatitis D virus (HDV), contains a small (approximately 1.7 kb) highly self-pairing single-strand circular RNA genome that assembles with the HDV antigen to form a ribonucleoprotein (RNP) complex. HDV depends on hepatitis B virus (HBV) envelope proteins for envelopment and de novo hepatocyte entry; however, its intracellular RNA replication is autonomous. In addition, HDV can amplify HBV independently through cell division. Cellular innate immune responses, mainly interferon (IFN) response, are crucial for controlling invading viruses, while viruses counteract these responses to favor their propagation. In contrast to HBV, HDV activates profound IFN response through the melanoma differentiation antigen 5 (MDA5) pathway. This cellular response efficiently suppresses cell-division-mediated HDV spread and, to some extent, early stages of HDV de novo infection, but only marginally impairs RNA replication in resting hepatocytes. In this review, we summarize the current knowledge on HDV structure, replication, and persistence and subsequently focus on the interplay between HDV and IFN response, including IFN activation, sensing, antiviral effects, and viral countermeasures. Finally, we discuss crosstalk with HBV.

show abstract

Section: Hdv Structure Replication and Persistencementioning

confidence: 99%

Interplay between Hepatitis D Virus and the Interferon Response

Zhang

Urban

2020

Viruses

View full text Add to dashboard Cite

show abstract

“…The ligated circular RNA (circRNA) is further transcribed into multimeric genomic RNAs which also undergo self-cleavage and ligation ( 4 ). Remarkably, HDV RNA replication is performed by cellular RNA polymerase II (Pol-II), with S-HDAg being essential in this process, as it coactivates Pol-II by possibly acting as a histone mimic ( 5 ). The RNA genome of HDV folds into an unbranched rod-like structure due to its high degree of self-complementarity ( 6 ).…”

mentioning

confidence: 99%

Mammalian deltavirus without hepadnavirus coinfection in the neotropical rodent Proechimys semispinosus

Paraskevopoulou

Fabian

Goldmann

et al. 2020

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

102

View full text Add to dashboard Cite

Hepatitis delta virus (HDV) is a human hepatitis-causing RNA virus, unrelated to any other taxonomic group of RNA viruses. Its occurrence as a satellite virus of hepatitis B virus (HBV) is a singular case in animal virology for which no consensus evolutionary explanation exists. Here we present a mammalian deltavirus that does not occur in humans, identified in the neotropical rodent species Proechimys semispinosus. The rodent deltavirus is highly distinct, showing a common ancestor with a recently described deltavirus in snakes. Reverse genetics based on a tandem minus-strand complementary DNA genome copy under the control of a cytomegalovirus (CMV) promoter confirms autonomous genome replication in transfected cells, with initiation of replication from the upstream genome copy. In contrast to HDV, a large delta antigen is not expressed and the farnesylation motif critical for HBV interaction is absent from a genome region that might correspond to a hypothetical rodent large delta antigen. Correspondingly, there is no evidence for coinfection with an HBV-related hepadnavirus based on virus detection and serology in any deltavirus-positive animal. No other coinfecting viruses were detected by RNA sequencing studies of 120 wild-caught animals that could serve as a potential helper virus. The presence of virus in blood and pronounced detection in reproductively active males suggest horizontal transmission linked to competitive behavior. Our study establishes a nonhuman, mammalian deltavirus that occurs as a horizontally transmitted infection, is potentially cleared by immune response, is not focused in the liver, and possibly does not require helper virus coinfection.

show abstract

“…Recent studies have shown that viral sequences mimic those of their hosts, to some extent, in part to evade immune responses (32,(50)(51), and this can be used to predict viral hosts (33). To this end, we set out to survey virus genomes and proteins and investigate whether the scenario of RAWs fits with our previous human-derived findings.…”

Section: Relative Absent Words and Nullomers In Virusesmentioning

confidence: 92%

Significant non-existence of sequences in genomes and proteomes

Koulouras

Frith

2020

Preprint

View full text Add to dashboard Cite

Nullomers are minimal-length oligomers absent from a genome or proteome. Although research has shown that artificially synthesized nullomers have deleterious effects, there is still a lack of a strategy for the prioritisation and classification of non-occurring sequences as potentially malicious or benign. In this work, by using Markovian models with multiple-testing correction, we reveal significant absent oligomers which are statistically expected to exist. This strongly suggests that their absence is due to negative selection. We survey genomes and proteomes covering the diversity of life, and find thousands of significant absent sequences. Common significant nullomers are often mono-or dinucleotide tracts, or palindromic. Significant viral nullomers are often restriction sites, and may indicate unknown restriction motifs. Surprisingly, significant mammal genome nullomers are often present, but rare, in other mammals, suggesting that they are suppressed but not completely forbidden. Significant human nullomers are rarely present in human viruses, indicating viral mimicry of the host. More than 1/4 of human proteins are one substitution away from containing a significant nullomer. We provide a webbased, interactive database of significant nullomers across genomes and proteomes.In this study, we introduce a robust probabilistic method named Nullomers Assessor (https://github.com/gkoulouras/nullomers-assessor) for the evaluation of globally missing sets of oligomers in any species, considering the fact that biological sequences of living organisms are driven by mutational biases and natural selection, and consequently are not entirely random (10). Naturally occurring sequences present patterns and combinatoric properties which can be signatures for the identification of functional elements as such promoters, tandem repeat expansions, introns, exons, and regulatory elements (18). In addition, evolutionarily well-separated species are known to possess distinct statistical characteristics in their DNA or peptide sequence chains (19). All these distinctive properties of biological sequences have frequently been studied using probabilistic models. Markov chain models have been widely and successfully employed in various biological problems including sequence analysis in the past (26-29). Taking advantage of these particular properties of biological sequences, we developed a method which approximates the likelihood of an absent sequence to occur exactly zero times, in order to address the following three questions. First, are there statistically significant minimal absent sequences in biological species; in simple words, what is the expected probability for an actual nullomer to be indeed absent, based on the compositional pattern in the full genome or proteome of a species? Second, are there significant MAWs in common across evolutionarily diverse living organisms? And finally, does the creation of a previously absent sequence perturb a molecule; more precisely, are there mutations with functional or stability impact ...

show abstract

Hepatitis Delta Virus histone mimicry drives the recruitment of chromatin remodelers for viral RNA replication

Cited by 19 publications

References 51 publications

Interplay between Hepatitis D Virus and the Interferon Response

Interplay between Hepatitis D Virus and the Interferon Response

Mammalian deltavirus without hepadnavirus coinfection in the neotropical rodent Proechimys semispinosus

Significant non-existence of sequences in genomes and proteomes

Contact Info

Product

Resources

About