scholarly journals Mutation bias implicates RNA editing in a wide range of mammalian RNA viruses

2021 ◽  
Author(s):  
Peter Simmonds ◽  
M. Azim Ansari
Keyword(s):  
Rna Editing ◽  
Rna Viruses ◽  
Rna Virus ◽  
Structural Parameters ◽  
Rapid Evolution ◽  
Sequence Variability ◽  
Diverse Range ◽  
Mouth Disease Virus ◽  
Wide Range ◽  
Virus Sequence

ABSTRACTThe rapid evolution of RNA viruses has been long considered to result from a combination of high copying error frequencies during RNA replication, short generation times and the consequent extensive fixation of neutral or adaptive changes over short periods. While both the identities and sites of mutations are typically modelled as being random, recent investigations of sequence diversity of SARS coronavirus 2 (SARS-CoV-2) have identified a preponderance of C->U transitions, potentially driven by an APOBEC-like RNA editing process. The current study investigated whether this phenomenon could be observed in the more genetically diverse datasets of other RNA viruses. Using a 5% divergence filter to infer directionality, 18 from 32 datasets of aligned coding region sequences from a diverse range of mammalian RNA viruses (including Picornaviridae, Flaviviridae, Matonaviridae, Caliciviridae and Coronaviridae) showed a >2-fold base composition normalised excess of C->U transitions compared to U->C (range 2.1x–7.5x). C->U transitions showed a favoured 5’ U upstream context consistent with previous analyses of APOBEC-mediated RNA targeting. Amongst several genomic compositional and structural parameters, the presence of genome scale RNA secondary structure (GORS) was associated with C->U/U->C transition asymmetries (p < 0.001), potentially reflecting the documented structure dependence of APOBEC-mediated RNA editing. Using the association index metric, C->U changes were specifically over-represented at phylogenetically uninformative sites, consistent with extensive homoplasy documented in SARS-CoV-2. Excess C->U substitutions accounted for 15-20% of standing sequence variability of HCV and other RNA viruses; RNA editing may therefore represent a potent driver of RNA virus sequence diversification and longer term evolution.Author SummaryThe rapid evolution of RNA viruses is thought to arise from high mutation frequencies during replication and the rapid accumulation of genetic changes over time in response to its changing environments. This study describes an additional potent factor that contributes to the evolution of RNA infecting mammals, the deliberate mutation of the viral genome by host antiviral pathways active within the cell when it becomes infected. This so called “genome editing” by one or more APOBEC enzymes leads to characteristic C->U mutations that damage the virus’s ability to replicate. While this pathway is well characterised as an antiviral defence against HIV and other retroviruses, this study provides evidence for its activity against a wide range of human and veterinary viruses, including HCV and foot and mouth disease virus. APOBEC-driven mutations accounted for 15-20% of standing sequence variability of RNA virus groups, representing a potent driver of RNA virus sequence diversification.

scholarly journals Extensive C->U transition biases in the genomes of a wide range of mammalian RNA viruses; potential associations with transcriptional mutations, damage- or host-mediated editing of viral RNA

2021 ◽  
Vol 17 (6) ◽  
pp. e1009596
Author(s):  
Peter Simmonds ◽  
M. Azim Ansari
Keyword(s):  
Rna Structure ◽  
Rna Viruses ◽  
Multivariable Analysis ◽  
Rapid Evolution ◽  
Structural Parameter ◽  
Coding Region ◽  
Association Index ◽  
Diverse Range ◽  
Wide Range ◽  
Genome Scale

The rapid evolution of RNA viruses has been long considered to result from a combination of high copying error frequencies during RNA replication, short generation times and the consequent extensive fixation of neutral or adaptive changes over short periods. While both the identities and sites of mutations are typically modelled as being random, recent investigations of sequence diversity of SARS coronavirus 2 (SARS-CoV-2) have identified a preponderance of C->U transitions, proposed to be driven by an APOBEC-like RNA editing process. The current study investigated whether this phenomenon could be observed in datasets of other RNA viruses. Using a 5% divergence filter to infer directionality, 18 from 36 datasets of aligned coding region sequences from a diverse range of mammalian RNA viruses (including Picornaviridae, Flaviviridae, Matonaviridae, Caliciviridae and Coronaviridae) showed a >2-fold base composition normalised excess of C->U transitions compared to U->C (range 2.1x–7.5x), with a consistently observed favoured 5’ U upstream context. The presence of genome scale RNA secondary structure (GORS) was the only other genomic or structural parameter significantly associated with C->U/U->C transition asymmetries by multivariable analysis (ANOVA), potentially reflecting RNA structure dependence of sites targeted for C->U mutations. Using the association index metric, C->U changes were specifically over-represented at phylogenetically uninformative sites, potentially paralleling extensive homoplasy of this transition reported in SARS-CoV-2. Although mechanisms remain to be functionally characterised, excess C->U substitutions accounted for 11–14% of standing sequence variability of structured viruses and may therefore represent a potent driver of their sequence diversification and longer-term evolution.

scholarly journals Origins and Evolution of the Global RNA Virome

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Yuri I. Wolf ◽  
Darius Kazlauskas ◽  
Jaime Iranzo ◽  
Adriana Lucía-Sanz ◽  
Jens H. Kuhn ◽  
...  
Keyword(s):  
Plant Pathogens ◽  
Rna Viruses ◽  
Rna Virus ◽  
Phylogenomic Analysis ◽  
Rna Helicases ◽  
Sequence Alignments ◽  
Recent Advances ◽  
Wide Range ◽  
Positive Sense ◽  
Dsrna Viruses

ABSTRACTViruses with RNA genomes dominate the eukaryotic virome, reaching enormous diversity in animals and plants. The recent advances of metaviromics prompted us to perform a detailed phylogenomic reconstruction of the evolution of the dramatically expanded global RNA virome. The only universal gene among RNA viruses is the gene encoding the RNA-dependent RNA polymerase (RdRp). We developed an iterative computational procedure that alternates the RdRp phylogenetic tree construction with refinement of the underlying multiple-sequence alignments. The resulting tree encompasses 4,617 RNA virus RdRps and consists of 5 major branches; 2 of the branches include positive-sense RNA viruses, 1 is a mix of positive-sense (+) RNA and double-stranded RNA (dsRNA) viruses, and 2 consist of dsRNA and negative-sense (−) RNA viruses, respectively. This tree topology implies that dsRNA viruses evolved from +RNA viruses on at least two independent occasions, whereas −RNA viruses evolved from dsRNA viruses. Reconstruction of RNA virus evolution using the RdRp tree as the scaffold suggests that the last common ancestors of the major branches of +RNA viruses encoded only the RdRp and a single jelly-roll capsid protein. Subsequent evolution involved independent capture of additional genes, in particular, those encoding distinct RNA helicases, enabling replication of larger RNA genomes and facilitating virus genome expression and virus-host interactions. Phylogenomic analysis reveals extensive gene module exchange among diverse viruses and horizontal virus transfer between distantly related hosts. Although the network of evolutionary relationships within the RNA virome is bound to further expand, the present results call for a thorough reevaluation of the RNA virus taxonomy.IMPORTANCEThe majority of the diverse viruses infecting eukaryotes have RNA genomes, including numerous human, animal, and plant pathogens. Recent advances of metagenomics have led to the discovery of many new groups of RNA viruses in a wide range of hosts. These findings enable a far more complete reconstruction of the evolution of RNA viruses than was attainable previously. This reconstruction reveals the relationships between different Baltimore classes of viruses and indicates extensive transfer of viruses between distantly related hosts, such as plants and animals. These results call for a major revision of the existing taxonomy of RNA viruses.

scholarly journals Negative-sense RNA viruses: An underexplored platform for examining virus–host lipid interactions

2021 ◽  
Vol 32 (20) ◽  
pp. pe1
Author(s):  
Monica L. Husby ◽  
Robert V. Stahelin
Keyword(s):  
Host Cell ◽  
Rna Viruses ◽  
Life Cycles ◽  
Diverse Range ◽  
Membrane Biology ◽  
Wide Range ◽  
Range Of Functions ◽  
Pathogenic Viruses ◽  
Pathogenic Agents ◽  
Negative Sense

Viruses are pathogenic agents that can infect all varieties of organisms, including plants, animals, and humans. These microscopic particles are genetically simple as they encode a limited number of proteins that undertake a wide range of functions. While structurally distinct, viruses often share common characteristics that have evolved to aid in their infectious life cycles. A commonly underappreciated characteristic of many deadly viruses is a lipid envelope that surrounds their protein and genetic contents. Notably, the lipid envelope is formed from the host cell the virus infects. Lipid-enveloped viruses comprise a diverse range of pathogenic viruses, which often lead to high fatality rates and many lack effective therapeutics and/or vaccines. This perspective primarily focuses on the negative-sense RNA viruses from the order Mononegavirales, which obtain their lipid envelope from the host plasma membrane. Specifically, the perspective highlights the common themes of host cell lipid and membrane biology necessary for virus replication, assembly, and budding.

scholarly journals Discovery and Characterization of Actively Replicating DNA and Retro-Transcribing Viruses in Lower Vertebrate Hosts Based on RNA Sequencing

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1042
Author(s):  
Xin-Xin Chen ◽  
Wei-Chen Wu ◽  
Mang Shi
Keyword(s):  
Rna Sequencing ◽  
Rna Viruses ◽  
Rna Virus ◽  
Acute Infection ◽  
Sufficient Information ◽  
Lower Vertebrate ◽  
Diverse Range ◽  
New Findings ◽  
Active Transcription ◽  
Vertebrate Hosts

In a previous study, a metatranscriptomics survey of RNA viruses in several important lower vertebrate host groups revealed huge viral diversity, transforming the understanding of the evolution of vertebrate-associated RNA virus groups. However, the diversity of the DNA and retro-transcribing viruses in these host groups was left uncharacterized. Given that RNA sequencing is capable of revealing viruses undergoing active transcription and replication, we collected previously generated datasets associated with lower vertebrate hosts, and searched them for DNA and retro-transcribing viruses. Our results revealed the complete genome, or “core gene sets”, of 18 vertebrate-associated DNA and retro-transcribing viruses in cartilaginous fishes, ray-finned fishes, and amphibians, many of which had high abundance levels, and some of which showed systemic infections in multiple organs, suggesting active transcription or acute infection within the host. Furthermore, these new findings recharacterized the evolutionary history in the families Hepadnaviridae, Papillomaviridae, and Alloherpesviridae, confirming long-term virus–host codivergence relationships for these virus groups. Collectively, our results revealed reliable and sufficient information within metatranscriptomics sequencing to characterize not only RNA viruses, but also DNA and retro-transcribing viruses, and therefore established a key methodology that will help us to understand the composition and evolution of the total “infectome” within a diverse range of vertebrate hosts.

scholarly journals RNA Virus-Encoded miRNAs: Current Insights and Future Challenges

2021 ◽  
Vol 12 ◽  
Author(s):  
Asuka Nanbo ◽  
Wakako Furuyama ◽  
Zhen Lin
Keyword(s):  
Viral Replication ◽  
Rna Viruses ◽  
Current Knowledge ◽  
Rna Virus ◽  
Transcriptional Level ◽  
Emerging Viruses ◽  
Wide Range ◽  
Future Challenges ◽  
Eukaryotic Gene ◽  
Potential Applications

MicroRNAs are small non-coding RNAs that regulate eukaryotic gene expression at the post-transcriptional level and affect a wide range of biological processes. Over the past two decades, numerous virus-encoded miRNAs have been identified. Some of them are crucial for viral replication, whereas others can help immune evasion. Recent sequencing-based bioinformatics methods have helped identify many novel miRNAs, which are encoded by RNA viruses. Unlike the well-characterized DNA virus-encoded miRNAs, the role of RNA virus-encoded miRNAs remains controversial. In this review, we first describe the current knowledge of miRNAs encoded by various RNA viruses, including newly emerging viruses. Next, we discuss how RNA virus-encoded miRNAs might facilitate viral replication, immunoevasion, and persistence in their hosts. Last, we briefly discuss the challenges in the experimental methodologies and potential applications of miRNAs for diagnosis and therapeutics.

scholarly journals High-Resolution Metatranscriptomics Reveals the Ecological Dynamics of Mosquito-Associated RNA Viruses in Western Australia

2017 ◽  
Vol 91 (17) ◽  
Author(s):  
Mang Shi ◽  
Peter Neville ◽  
Jay Nicholson ◽  
John-Sebastian Eden ◽  
Allison Imrie ◽  
...  
Keyword(s):  
Western Australia ◽  
Rna Viruses ◽  
Rna Virus ◽  
Geographic Location ◽  
Striking Difference ◽  
Sampling Location ◽  
Virus Species ◽  
Diverse Range ◽  
Content Type ◽  
Virus Diversity

ABSTRACT Mosquitoes harbor a high diversity of RNA viruses, including many that impact human health. Despite a growing effort to describe the extent and nature of the mosquito virome, little is known about how these viruses persist, spread, and interact with both their hosts and other microbes. To address this issue we performed a metatranscriptomics analysis of 12 Western Australian mosquito populations structured by species and geographic location. Our results identified the complete genomes of 24 species of RNA viruses from a diverse range of viral families and orders, among which 19 are newly described. Comparisons of viromes revealed a striking difference between the two mosquito genera, with viromes of mosquitoes of the Aedes genus exhibiting substantially less diversity and lower abundances than those of mosquitoes of the Culex genus, within which the viral abundance reached 16.87% of the total non-rRNA. In addition, there was little overlap in viral diversity between the two genera, although the viromes were very similar among the three Culex species studied, suggesting that the host taxon plays a major role in structuring virus diversity. In contrast, we found no evidence that geographic location played a major role in shaping RNA virus diversity, and several viruses discovered here exhibited high similarity (95 to 98% nucleotide identity) to those from Indonesia and China. Finally, using abundance-level and phylogenetic relationships, we were able to distinguish potential mosquito viruses from those present in coinfecting bacteria, fungi, and protists. In sum, our metatranscriptomics approach provides important insights into the ecology of mosquito RNA viruses. IMPORTANCE Studies of virus ecology have generally focused on individual viral species. However, recent advances in bulk RNA sequencing make it possible to utilize metatranscriptomic approaches to reveal both complete virus diversity and the relative abundance of these viruses. We used such a metatranscriptomic approach to determine key aspects of the ecology of mosquito viruses in Western Australia. Our results show that RNA viruses are some of the most important components of the mosquito transcriptome, and we identified 19 new virus species from a diverse set of virus families. A key result was that host genetic background plays a more important role in shaping virus diversity than sampling location, with Culex species harboring more viruses at higher abundance than those from Aedes mosquitoes.

scholarly journals Origins and Evolution of the Global RNA Virome

2018 ◽  
Author(s):  
Yuri I. Wolf ◽  
Darius Kazlauskas ◽  
Jaime Iranzo ◽  
Adriana LucÍa-Sanz ◽  
Jens H. Kuhn ◽  
...  
Keyword(s):  
Plant Pathogens ◽  
Rna Viruses ◽  
Rna Virus ◽  
Phylogenomic Analysis ◽  
Rna Helicases ◽  
Sequence Alignments ◽  
Recent Advances ◽  
Wide Range ◽  
Positive Sense ◽  
Dsrna Viruses

AbstractViruses with RNA genomes dominate the eukaryotic virome, reaching enormous diversity in animals and plants. The recent advances of metaviromics prompted us to perform a detailed phylogenomic reconstruction of the evolution of the dramatically expanded global RNA virome. The only universal gene among RNA viruses is the RNA-dependent RNA polymerase (RdRp). We developed an iterative computational procedure that alternates the RdRp phylogenetic tree construction with refinement of the underlying multiple sequence alignments. The resulting tree encompasses 4,617 RNA virus RdRps and consists of 5 major branches, 2 of which include positive-sense RNA viruses, 1 is a mix of positive-sense (+) RNA and double-stranded (ds) RNA viruses, and 2 consist of dsRNA and negative-sense (−) RNA viruses, respectively. This tree topology implies that dsRNA viruses evolved from +RNA viruses on at least two independent occasions, whereas -RNA viruses evolved from dsRNA viruses. Reconstruction of RNA virus evolution using the RdRp tree as the scaffold suggests that the last common ancestors of the major branches of +RNA viruses encoded only the RdRp and a single jelly-roll capsid protein. Subsequent evolution involved independent capture of additional genes, particularly, those encoding distinct RNA helicases, enabling replication of larger RNA genomes and facilitating virus genome expression and virus-host interactions. Phylogenomic analysis reveals extensive gene module exchange among diverse viruses and horizontal virus transfer between distantly related hosts. Although the network of evolutionary relationships within the RNA virome is bound to further expand, the present results call for a thorough reevaluation of the RNA virus taxonomy.IMPORTANCEThe majority of the diverse viruses infecting eukaryotes have RNA genomes, including numerous human, animal, and plant pathogens. Recent advances of metagenomics have led to the discovery of many new groups of RNA viruses in a wide range of hosts. These findings enable a far more complete reconstruction of the evolution of RNA viruses than what was attainable previously. This reconstruction reveals the relationships between different Baltimore Classes of viruses and indicates extensive transfer of viruses between distantly related hosts, such as plants and animals. These results call for a major revision of the existing taxonomy of RNA viruses.

Early Generation Pipeline Girth Welding Practices and Their Implications for Integrity Management of North American Pipelines

2010 ◽  
Author(s):  
Bill Amend
Keyword(s):  
Brittle Fracture ◽  
Rapid Evolution ◽  
Charpy Impact ◽  
Mechanical Tests ◽  
Impact Testing ◽  
Early Generation ◽  
Diverse Range ◽  
Integrity Assessment ◽  
Wide Range ◽  
Girth Welds

The characteristics of early generation pipelines (i.e., “vintage pipelines”) reflect the rapid evolution of pipeline materials, welding, and inspection practices that occurred during the first half of the twentieth century. The diverse range of welding and inspection practices and the unique characteristics of early generation pipeline welds can influence pipeline segment risk ranking and integrity assessment. This paper summarizes some of the key findings regarding girth weld fabrication, performance and integrity assessment determined during the course of a literature review performed as part of a recently completed PRCI project. Some of the key findings include: 1. The failure rate of early generation girth welds is low, particularly for welds made by arc welding and for welds made after 1930. This is especially true when considering the rate of catastrophic failures (ruptures or nearly full circumference breaks). Welds are typically reported to be responsible for no more than about 6% of significant pipeline failures. 2. Pipeline girth welds are unlikely to fail unless subjected to axial strains that far exceed the strains related to internal pressure alone. Girth welds containing significant workmanship flaws are likely to be resistant to failure at stresses less than the pipe yield strength unless the welds are undermatched and/or are susceptible to brittle fracture initiation. Common mechanical tests, such as Charpy impact testing or CTOD tests may result in grossly conservative indications of the likelihood of brittle fracture occurring in vintage girth welds. 3. A diverse range of early generation girth weld joint designs exist, some of which hamper effective inspection using ILI or represent challenges to effective assessment using conventional fitness-for-service or engineering critical assessment methods (ECA). Effective probabilistic ECA is further hampered by wide variations in workmanship and difficulty in determining mechanical property distributions. 4. Pipeline vintage is a poor indicator of girth weld integrity. Pipeline girth weld integrity is more likely related to project-specific inspection and testing practices than to pipeline age. Welding and inspection practices evolved very quickly in the 1920s through the 1940s and a wide range of practices were used on different pipelines that were constructed in the same time period. Girth weld integrity is typically highest for post 1930s pipelines that were subjected to radiographic inspection.

Nine Centuries of Man

2017 ◽  
Keyword(s):  
Twentieth Century ◽  
Diverse Range ◽  
Gender Expectations ◽  
Court Records ◽  
The Past ◽  
Wide Range ◽  
Police Reports ◽  
Late Twentieth ◽  
Scottish History ◽  
Late Twentieth Century

What did it mean to be a man in Scotland over the past nine centuries? Scotland, with its stereotypes of the kilted warrior and the industrial ‘hard man’, has long been characterised in masculine terms, but there has been little historical exploration of masculinity in a wider context. This interdisciplinary collection examines a diverse range of the multiple and changing forms of masculinities from the late eleventh to the late twentieth century, exploring the ways in which Scottish society through the ages defined expectations for men and their behaviour. How men reacted to those expectations is examined through sources such as documentary materials, medieval seals, romances, poetry, begging letters, police reports and court records, charity records, oral histories and personal correspondence. Focusing upon the wide range of activities and roles undertaken by men – work, fatherhood and play, violence and war, sex and commerce – the book also illustrates the range of masculinities that affected or were internalised by men. Together, the chapters illustrate some of the ways Scotland’s gender expectations have changed over the centuries and how, more generally, masculinities have informed the path of Scottish history

Diversity and Integration in Private International Law

2019 ◽  
Keyword(s):  
South America ◽  
International Law ◽  
Value Systems ◽  
Private International Law ◽  
Diverse Range ◽  
Cross Border ◽  
Wide Range ◽  
Depth Analysis ◽  
And Shifts ◽  
Substantive Law

This book opens a cross-regional dialogue and shifts the Eurocentric discussion on diversity and integration to a more inclusive engagement with South America in private international law issues. It promotes a contemporary vision of private international law as a discipline enabling legal interconnectivity, with the potential to transcend its disciplinary boundaries to further promote the reality of cross-border integration, with its focus on the ever-increasing cross-border mobility of individuals. Private international law embraces legal diversity and pluralism. Different legal traditions continue to meet, interact and integrate in different forms, at the national, regional and international levels. Different systems of substantive law couple with divergent systems of private international law (designed to accommodate the former in cross-border situations). This complex legal landscape impacts individuals and families in cross-border scenarios, and international commerce broadly conceived. Private international law methodologies and techniques offer means for the coordination of this constellation of legal orders and value systems in cross-border situations. Bringing together world-renowned academics and experienced private international lawyers from a wide range of jurisdictions in Europe and South America, this edited collection focuses on the connective capabilities of private international law in bridging and balancing legal diversity as a corollary for the development of integration. The book provides in-depth analysis of the role of private international law in dealing with legal diversity across a diverse range of topics and jurisdictions.

Sign in / Sign up

Export Citation Format

Share Document