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Cell Feb 2023Viroids and viroid-like covalently closed circular (ccc) RNAs are minimal replicators that typically encode no proteins and hijack cellular enzymes for replication. The...
Viroids and viroid-like covalently closed circular (ccc) RNAs are minimal replicators that typically encode no proteins and hijack cellular enzymes for replication. The extent and diversity of viroid-like agents are poorly understood. We developed a computational pipeline to identify viroid-like cccRNAs and applied it to 5,131 metatranscriptomes and 1,344 plant transcriptomes. The search yielded 11,378 viroid-like cccRNAs spanning 4,409 species-level clusters, a 5-fold increase compared to the previously identified viroid-like elements. Within this diverse collection, we discovered numerous putative viroids, satellite RNAs, retrozymes, and ribozy-like viruses. Diverse ribozyme combinations and unusual ribozymes within the cccRNAs were identified. Self-cleaving ribozymes were identified in ambiviruses, some mito-like viruses and capsid-encoding satellite virus-like cccRNAs. The broad presence of viroid-like cccRNAs in diverse transcriptomes and ecosystems implies that their host range is far broader than currently known, and matches to CRISPR spacers suggest that some cccRNAs replicate in prokaryotes.
Topics: RNA, Circular; Viroids; RNA, Catalytic; RNA, Viral; Ecosystem; Plant Diseases
PubMed: 36696902
DOI: 10.1016/j.cell.2022.12.039 -
Molecular Plant-microbe Interactions :... Mar 2016Satellite RNAs and satellite viruses are extraviral components that can affect either the pathogenicity, the accumulation, or both of their associated viruses while... (Review)
Review
Satellite RNAs and satellite viruses are extraviral components that can affect either the pathogenicity, the accumulation, or both of their associated viruses while themselves being dependent on the associated viruses as helper viruses for their infection. Most of these satellite RNAs are noncoding RNAs, and in many cases, have been shown to alter the interaction of their helper viruses with their hosts. In only a few cases have the functions of these satellite RNAs in such interactions been studied in detail. In particular, work on the satellite RNAs of Cucumber mosaic virus and Turnip crinkle virus have provided novel insights into RNAs functioning as noncoding RNAs. These effects are described and potential roles for satellite RNAs in the processes involved in symptom intensification or attenuation are discussed. In most cases, models describing these roles involve some aspect of RNA silencing or its suppression, either directly or indirectly involving the particular satellite RNA.
Topics: Cucumber Mosaic Virus Satellite; Cucumovirus; Gene Expression Regulation, Viral; RNA, Satellite; Satellite Viruses
PubMed: 26551994
DOI: 10.1094/MPMI-10-15-0232-FI -
Nature Communications Nov 2021The success of many viruses depends upon cooperative interactions between viral genomes. However, whenever cooperation occurs, there is the potential for 'cheats' to... (Review)
Review
The success of many viruses depends upon cooperative interactions between viral genomes. However, whenever cooperation occurs, there is the potential for 'cheats' to exploit that cooperation. We suggest that: (1) the biology of viruses makes viral cooperation particularly susceptible to cheating; (2) cheats are common across a wide range of viruses, including viral entities that are already well studied, such as defective interfering genomes, and satellite viruses. Consequently, the evolutionary theory of cheating could help us understand and manipulate viral dynamics, while viruses also offer new opportunities to study the evolution of cheating.
Topics: Evolution, Molecular; Genome, Viral; Host Microbial Interactions; Molecular Mimicry; Viruses
PubMed: 34836945
DOI: 10.1038/s41467-021-27293-6 -
Viruses Apr 2021Hepatitis Delta virus (HDV) lies in between satellite viruses and viroids, as its unique molecular characteristics and life cycle cannot categorize it according to the... (Review)
Review
Hepatitis Delta virus (HDV) lies in between satellite viruses and viroids, as its unique molecular characteristics and life cycle cannot categorize it according to the standard taxonomy norms for viruses. Being a satellite virus of hepatitis B virus (HBV), HDV requires HBV envelope glycoproteins for its infection cycle and its transmission. HDV pathogenesis varies and depends on the mode of HDV and HBV infection; a simultaneous HDV and HBV infection will lead to an acute hepatitis that will resolve spontaneously in the majority of patients, whereas an HDV super-infection of a chronic HBV carrier will mainly result in the establishment of a chronic HDV infection that may progress towards cirrhosis, liver decompensation, and hepatocellular carcinoma (HCC). With this review, we aim to unravel Ariadne's thread into the labyrinth of acute and chronic HDV infection pathogenesis and will provide insights into the complexity of this exciting topic by detailing the different players and mechanisms that shape the clinical outcome.
Topics: Animals; Carcinoma, Hepatocellular; Coinfection; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic; Hepatitis Delta Virus; Hepatitis delta Antigens; Humans; Liver Neoplasms; Mice; RNA, Viral; Satellite Viruses; Virus Replication
PubMed: 33924806
DOI: 10.3390/v13050778 -
Biochemistry Apr 2017The RNA genomes of viruses likely undergo multiple functionally important conformational changes during their replication cycles, changes that are poorly understood at...
The RNA genomes of viruses likely undergo multiple functionally important conformational changes during their replication cycles, changes that are poorly understood at present. We used two complementary in-solution RNA structure probing strategies (SHAPE-MaP and RING-MaP) to examine the structure of the RNA genome of satellite tobacco mosaic virus inside authentic virions and in a capsid-free state. Both RNA states feature similar three-domain architectures in which each major replicative function-translation, capsid coding, and genome synthesis-fall into distinct domains. There are, however, large conformational differences between the in-virion and capsid-free states, primarily in one arm of the central T domain. These data support a model in which the packaged capsid-bound RNA is constrained in a local high-energy conformation by the native capsid shell. The removal of the viral capsid then allows the RNA genome to relax into a more thermodynamically stable conformation. The RNA architecture of the central T domain thus likely changes during capsid assembly and disassembly and may play a role in genome packaging.
Topics: Genome, Viral; Models, Chemical; Nucleic Acid Conformation; RNA, Viral; Tobacco Mosaic Virus; Virus Assembly
PubMed: 28332826
DOI: 10.1021/acs.biochem.6b01166 -
Viruses Jan 2023Vaccination has been confirmed to be the safest and, sometimes, the only tool of defense against threats from infectious diseases. The successful history of vaccination... (Review)
Review
Vaccination has been confirmed to be the safest and, sometimes, the only tool of defense against threats from infectious diseases. The successful history of vaccination is evident in the control of serious viral infections, such as smallpox and polio. Viruses that infect human livers are known as hepatitis viruses and are classified into five major types from A to E, alphabetically. Although infection with hepatitis A virus (HAV) is known to be self-resolving after rest and symptomatic treatment, there were 7134 deaths from HAV worldwide in 2016. In 2019, hepatitis B virus (HBV) and hepatitis C virus (HCV) resulted in an estimated 820,000 and 290,000 deaths, respectively. Hepatitis delta virus (HDV) is a satellite virus that depends on HBV for producing its infectious particles in order to spread. The combination of HDV and HBV infection is considered the most severe form of chronic viral hepatitis. Hepatitis E virus (HEV) is another orally transmitted virus, common in low- and middle-income countries. In 2015, it caused 44,000 deaths worldwide. Safe and effective vaccines are already available to prevent hepatitis A and B. Here, we review the recent advances in protective vaccines against the five major hepatitis viruses.
Topics: Humans; Hepatitis Viruses; Hepatitis A; Hepatitis C; Hepatitis B; Hepatitis B virus; Hepatitis A virus; Hepatitis Delta Virus; Vaccines
PubMed: 36680254
DOI: 10.3390/v15010214 -
Frontiers in Microbiology 2021Hepatitis delta virus (HDV) is a human pathogen, and the only known species in the genus . HDV is a satellite virus and depends on the hepatitis B virus (HBV) for... (Review)
Review
Hepatitis delta virus (HDV) is a human pathogen, and the only known species in the genus . HDV is a satellite virus and depends on the hepatitis B virus (HBV) for packaging, release, and transmission. Extracellular HDV virions contain the genomic HDV RNA, a single-stranded negative-sense and covalently closed circular RNA molecule, which is associated with the HDV-encoded delta antigen forming a ribonucleoprotein complex, and enveloped by the HBV surface antigens. Replication occurs in the nucleus and is mediated by host enzymes and assisted by -acting ribozymes allowing the formation of monomer length molecules which are ligated by host ligases to form unbranched rod-like circles. Recently, meta-transcriptomic studies investigating various vertebrate and invertebrate samples identified RNA species with similarities to HDV RNA. The delta-like agents may be representatives of novel subviral agents or satellite viruses which share with HDV, the self-complementarity of the circular RNA genome, the ability to encode a protein, and the presence of ribozyme sequences. The widespread distribution of delta-like agents across different taxa with considerable phylogenetic distances may be instrumental in comprehending their evolutionary history by elucidating the transition from transcriptome to cellular circular RNAs to infectious subviral agents.
PubMed: 34234753
DOI: 10.3389/fmicb.2021.652962 -
Viruses Dec 2018Hepatitis delta virus (HDV) is unique among animal viruses. HDV is a satellite virus of the hepatitis B virus (HBV), however it shares no sequence similarity with its... (Review)
Review
Hepatitis delta virus (HDV) is unique among animal viruses. HDV is a satellite virus of the hepatitis B virus (HBV), however it shares no sequence similarity with its helper virus and replicates independently in infected cells. HDV is the smallest human pathogenic RNA virus and shares numerous characteristics with viroids. Like viroids, HDV has a circular RNA genome which adopts a rod-like secondary structure, possesses ribozyme domains, replicates in the nucleus of infected cells by redirecting host DNA-dependent RNA polymerases (RNAP), and relies heavily on host proteins for its replication due to its small size and limited protein coding capacity. These similarities suggest an evolutionary relationship between HDV and viroids, and information on HDV could allow a better understanding of viroids and might globally help understanding the pathogenesis and molecular biology of these subviral RNAs. In this review, we discuss the host involvement in HDV replication and its implication for HDV pathogenesis.
Topics: DNA Replication; DNA-Directed RNA Polymerases; Genome, Viral; Hepatitis B virus; Hepatitis Delta Virus; Host-Pathogen Interactions; Humans; RNA; RNA, Circular; RNA, Viral; Satellite Viruses; Viroids; Virus Replication
PubMed: 30602655
DOI: 10.3390/v11010021 -
Annual Review of Virology Sep 2022My early life was challenging, and not conducive to the study of science, but my first introduction to viruses was an epiphany for me. I spent the whole of my career... (Review)
Review
My early life was challenging, and not conducive to the study of science, but my first introduction to viruses was an epiphany for me. I spent the whole of my career dedicated to understanding viruses, driven largely by curiosity. This led me down many different avenues of study, and to work with many wonderful colleagues, most of whom remain friends. Some highlights of my career include the discovery of a mutualistic three-way symbiosis involving a virus, a fungus, and a plant; genetic mapping of a pathogenicity gene in tomato; uncovering a virus in 1,000-year-old corncobs; exploring virus biodiversity in wild plants; and establishing a system to use a fungal virus to understand the epidemiology of its host.
Topics: Biodiversity; Exploratory Behavior; Humans; Infant, Newborn; Plants; Symbiosis
PubMed: 35512631
DOI: 10.1146/annurev-virology-100520-013446 -
Viruses Jan 2022The hepatitis delta virus (HDV) is the smallest known human virus, yet it causes great harm to patients co-infected with hepatitis B virus (HBV). As a satellite virus of... (Review)
Review
The hepatitis delta virus (HDV) is the smallest known human virus, yet it causes great harm to patients co-infected with hepatitis B virus (HBV). As a satellite virus of HBV, HDV requires the surface antigen of HBV (HBsAg) for sufficient viral packaging and spread. The special circumstance of co-infection, albeit only one partner depends on the other, raises many virological, immunological, and pathophysiological questions. In the last years, breakthroughs were made in understanding the adaptive immune response, in particular, virus-specific CD4+ and CD8+ T cells, in self-limited versus persistent HBV/HDV co-infection. Indeed, the mechanisms of CD8+ T cell failure in persistent HBV/HDV co-infection include viral escape and T cell exhaustion, and mimic those in other persistent human viral infections, such as hepatitis C virus (HCV), human immunodeficiency virus (HIV), and HBV mono-infection. However, compared to these larger viruses, the small HDV has perfectly adapted to evade recognition by CD8+ T cells restricted by common human leukocyte antigen (HLA) class I alleles. Furthermore, accelerated progression towards liver cirrhosis in persistent HBV/HDV co-infection was attributed to an increased immune-mediated pathology, either caused by innate pathways initiated by the interferon (IFN) system or triggered by misguided and dysfunctional T cells. These new insights into HDV-specific adaptive immunity will be discussed in this review and put into context with known well-described aspects in HBV, HCV, and HIV infections.
Topics: Adaptive Immunity; Animals; CD8-Positive T-Lymphocytes; Hepatitis D; Hepatitis Delta Virus; Humans; Immune Evasion; Virus Replication
PubMed: 35215790
DOI: 10.3390/v14020198