scholarly journals Epistasis between mutations is host-dependent for an RNA virus

2013 ◽  
Vol 9 (1) ◽  
pp. 20120396 ◽  
Author(s):  
Jasna Lalić ◽  
Santiago F. Elena
Keyword(s):  
Infectious Diseases ◽  
Host Species ◽  
Evolutionary Ecology ◽  
Environmental Changes ◽  
Rna Viruses ◽  
Rna Virus ◽  
Emerging Viruses ◽  
Viral Emergence ◽  
Overlapping Reading Frames ◽  
Reading Frames

How, and to what extent, does the environment influence the way mutations interact? Do environmental changes affect both the sign and the magnitude of epistasis? Are there any correlations between environments in the variability, sign or magnitude of epistasis? Very few studies have tackled these questions. Here, we addressed them in the context of viral emergence. Most emerging viruses are RNA viruses with small genomes, overlapping reading frames and multifunctional proteins for which epistasis is abundant. Understanding the effect of host species in the sign and magnitude of epistasis will provide insights into the evolutionary ecology of infectious diseases and the predictability of viral emergence.

scholarly journals Tissue Tropism and Transmission Ecology Predict Virulence of Human RNA Viruses

2019 ◽  
Author(s):  
Liam Brierley ◽  
Amy B. Pedersen ◽  
Mark E. J. Woolhouse
Keyword(s):  
Public Health ◽  
Machine Learning ◽  
Risk Factors ◽  
Random Forest ◽  
Infectious Diseases ◽  
Rna Viruses ◽  
Rna Virus ◽  
Tissue Tropism ◽  
Virus Species ◽  
Ecological Traits

AbstractNovel infectious diseases continue to emerge within human populations. Predictive studies have begun to identify pathogen traits associated with emergence. However, emerging pathogens vary widely in virulence, a key determinant of their ultimate risk to public health. Here, we use structured literature searches to review the virulence of each of the 214 known human-infective RNA virus species. We then use a machine learning framework to determine whether viral virulence can be predicted by ecological traits including human-to-human transmissibility, transmission routes, tissue tropisms and host range. Using severity of clinical disease as a measurement of virulence, we identified potential risk factors using predictive classification tree and random forest ensemble models. The random forest model predicted literature-assigned disease severity of test data with 90.3% accuracy, compared to a null accuracy of 74.2%. In addition to viral taxonomy, the ability to cause systemic infection, having renal and/or neural tropism, direct contact or respiratory transmission, and limited (0 < R0 ≤ 1) human-to-human transmissibility were the strongest predictors of severe disease. We present a novel, comparative perspective on the virulence of all currently known human RNA virus species. The risk factors identified may provide novel perspectives in understanding the evolution of virulence and elucidating molecular virulence mechanisms. These risk factors could also improve planning and preparedness in public health strategies as part of a predictive framework for novel human infections.Author SummaryNewly emerging infectious diseases present potentially serious threats to global health. Although studies have begun to identify pathogen traits associated with the emergence of new human diseases, these do not address why emerging infections vary in the severity of disease they cause, often termed ‘virulence’. We test whether ecological traits of human viruses can act as predictors of virulence, as suggested by theoretical studies. We conduct the first systematic review of virulence across all currently known human RNA virus species. We adopt a machine learning approach by constructing a random forest, a model that aims to optimally predict an outcome using a specific structure of predictors. Predictions matched literature-assigned ratings for 28 of 31 test set viruses. Our predictive model suggests that higher virulence is associated with infection of multiple organ systems, nervous systems or the renal systems. Higher virulence was also associated with contact-based or airborne transmission, and limited capability to transmit between humans. These risk factors may provide novel starting points for questioning why virulence should evolve and identifying causative mechanisms of virulence. In addition, our work could suggest priority targets for infectious disease surveillance and future public health risk strategies.BlurbComparative analysis using machine learning shows specificity of tissue tropism and transmission biology can act as predictive risk factors for virulence of human RNA viruses.

scholarly journals Viral evolution and the emergence of SARS coronavirus

2004 ◽  
Vol 359 (1447) ◽  
pp. 1059-1065 ◽  
Author(s):  
Edward C. Holmes ◽  
Andrew Rambaut
Keyword(s):  
Genetic Factors ◽  
Rna Viruses ◽  
Viral Evolution ◽  
Emerging Diseases ◽  
Species Boundaries ◽  
Emerging Viruses ◽  
New Host ◽  
Viral Emergence ◽  
Mechanistic Basis ◽  
New Host Species

The recent appearance of severe acute respiratory syndrome coronavirus (SARS–CoV) highlights the continual threat to human health posed by emerging viruses. However, the central processes in the evolution of emerging viruses are unclear, particularly the selection pressures faced by viruses in new host species. We outline some of the key evolutionary genetic aspects of viral emergence. We emphasize that, although the high mutation rates of RNA viruses provide them with great adaptability and explain why they are the main cause of emerging diseases, their limited genome size means that they are also subject to major evolutionary constraints. Understanding the mechanistic basis of these constraints, particularly the roles played by epistasis and pleiotropy, is likely to be central in explaining why some RNA viruses are more able than others to cross species boundaries. Viral genetic factors have also been implicated in the emergence of SARS–CoV, with the suggestion that this virus is a recombinant between mammalian and avian coronaviruses. We show, however, that the phylogenetic patterns cited as evidence for recombination are more probably caused by a variation in substitution rate among lineages and that recombination is unlikely to explain the appearance of SARS in humans.

scholarly journals RNA Viruses in Aquatic Unicellular Eukaryotes

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 362
Author(s):  
Mohammadreza Sadeghi ◽  
Yuji Tomaru ◽  
Tero Ahola
Keyword(s):  
Host Species ◽  
Rna Viruses ◽  
Rna Virus ◽  
Sequence Information ◽  
Virus Species ◽  
Ecological Role ◽  
Major Fraction ◽  
Marine Virus ◽  
Unicellular Eukaryotes

Increasing sequence information indicates that RNA viruses constitute a major fraction of marine virus assemblages. However, only 12 RNA virus species have been described, infecting known host species of marine single-celled eukaryotes. Eight of these use diatoms as hosts, while four are resident in dinoflagellate, raphidophyte, thraustochytrid, or prasinophyte species. Most of these belong to the order Picornavirales, while two are divergent and fall into the families Alvernaviridae and Reoviridae. However, a very recent study has suggested that there is extraordinary diversity in aquatic RNA viromes, describing thousands of viruses, many of which likely use protist hosts. Thus, RNA viruses are expected to play a major ecological role for marine unicellular eukaryotic hosts. In this review, we describe in detail what has to date been discovered concerning viruses with RNA genomes that infect aquatic unicellular eukaryotes.

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 Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform

2020 ◽  
Author(s):  
Tran Thi Nhu Thao ◽  
Fabien Labroussaa ◽  
Nadine Ebert ◽  
Philip V’kovski ◽  
Hanspeter Stalder ◽  
...  
Keyword(s):  
Reverse Genetics ◽  
Yeast Artificial Chromosome ◽  
Vaccine Development ◽  
Rna Viruses ◽  
Rna Virus ◽  
Functional Characterization ◽  
Clinical Samples ◽  
Emerging Viruses ◽  
Synthetic Dna ◽  
Synthetic Genomics

AbstractReverse genetics has been an indispensable tool revolutionising our insights into viral pathogenesis and vaccine development. Large RNA virus genomes, such as from Coronaviruses, are cumbersome to clone and to manipulate in E. coli hosts due to size and occasional instability1-3. Therefore, an alternative rapid and robust reverse genetics platform for RNA viruses would benefit the research community. Here we show the full functionality of a yeast-based synthetic genomics platform for the genetic reconstruction of diverse RNA viruses, including members of the Coronaviridae, Flaviviridae and Paramyxoviridae families. Viral subgenomic fragments were generated using viral isolates, cloned viral DNA, clinical samples, or synthetic DNA, and reassembled in one step in Saccharomyces cerevisiae using transformation associated recombination (TAR) cloning to maintain the genome as a yeast artificial chromosome (YAC). T7-RNA polymerase has been used to generate infectious RNA, which was then used to rescue viable virus. Based on this platform we have been able to engineer and resurrect chemically-synthetized clones of the recent epidemic SARS-CoV-24 in only a week after receipt of the synthetic DNA fragments. The technical advance we describe here allows to rapidly responding to emerging viruses as it enables the generation and functional characterization of evolving RNA virus variants - in real-time - during an outbreak.

Mechanisms and Concepts in RNA Virus Population Dynamics and Evolution

2018 ◽  
Vol 5 (1) ◽  
pp. 69-92 ◽  
Author(s):  
Patrick T. Dolan ◽  
Zachary J. Whitfield ◽  
Raul Andino
Keyword(s):  
Evolutionary Dynamics ◽  
Environmental Changes ◽  
Rna Viruses ◽  
Rna Virus ◽  
Spatial And Temporal Scales ◽  
Immune Pressure ◽  
Pharmacological Challenge ◽  
Recent Developments ◽  
Relationship Of ◽  
The Relationship

RNA viruses are unique in their evolutionary capacity, exhibiting high mutation rates and frequent recombination. They rapidly adapt to environmental changes, such as shifts in immune pressure or pharmacological challenge. The evolution of RNA viruses has been brought into new focus with the recent developments of genetic and experimental tools to explore and manipulate the evolutionary dynamics of viral populations. These studies have uncovered new mechanisms that enable viruses to overcome evolutionary challenges in the environment and have emphasized the intimate relationship of viral populations with evolution. Here, we review some of the emerging viral and host mechanisms that underlie the evolution of RNA viruses. We also discuss new studies that demonstrate that the relationship between evolutionary dynamics and virus biology spans many spatial and temporal scales, affecting transmission dynamics within and between hosts as well as pathogenesis.

scholarly journals Structure Unveils Relationships between RNA Virus Polymerases

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 313
Author(s):  
Heli A. M. Mönttinen ◽  
Janne J. Ravantti ◽  
Minna M. Poranen
Keyword(s):  
Phylogenetic Tree ◽  
Rna Viruses ◽  
Rna Virus ◽  
Sequence Similarity ◽  
Protein Structures ◽  
Structural Similarity ◽  
Functional Differentiation ◽  
Comparison Method ◽  
Homologous Structure ◽  
Biological Entities

RNA viruses are the fastest evolving known biological entities. Consequently, the sequence similarity between homologous viral proteins disappears quickly, limiting the usability of traditional sequence-based phylogenetic methods in the reconstruction of relationships and evolutionary history among RNA viruses. Protein structures, however, typically evolve more slowly than sequences, and structural similarity can still be evident, when no sequence similarity can be detected. Here, we used an automated structural comparison method, homologous structure finder, for comprehensive comparisons of viral RNA-dependent RNA polymerases (RdRps). We identified a common structural core of 231 residues for all the structurally characterized viral RdRps, covering segmented and non-segmented negative-sense, positive-sense, and double-stranded RNA viruses infecting both prokaryotic and eukaryotic hosts. The grouping and branching of the viral RdRps in the structure-based phylogenetic tree follow their functional differentiation. The RdRps using protein primer, RNA primer, or self-priming mechanisms have evolved independently of each other, and the RdRps cluster into two large branches based on the used transcription mechanism. The structure-based distance tree presented here follows the recently established RdRp-based RNA virus classification at genus, subfamily, family, order, class and subphylum ranks. However, the topology of our phylogenetic tree suggests an alternative phylum level organization.

scholarly journals Fludarabine Inhibits Infection of Zika Virus, SFTS Phlebovirus, and Enterovirus A71

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 774
Author(s):  
Chengfeng Gao ◽  
Chunxia Wen ◽  
Zhifeng Li ◽  
Shuhan Lin ◽  
Shu Gao ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Zika Virus ◽  
Therapeutic Agent ◽  
Viral Infections ◽  
Rna Virus ◽  
Emerging Viruses ◽  
Enterovirus A71 ◽  
Ic50 Values ◽  
High Doses ◽  
Severe Fever

Viral infections are one of the leading causes in human mortality and disease. Broad-spectrum antiviral drugs are a powerful weapon against new and re-emerging viruses. However, viral resistance to existing broad-spectrum antivirals remains a challenge, which demands development of new broad-spectrum therapeutics. In this report, we showed that fludarabine, a fluorinated purine analogue, effectively inhibited infection of RNA viruses, including Zika virus, Severe fever with thrombocytopenia syndrome virus, and Enterovirus A71, with all IC50 values below 1 μM in Vero, BHK21, U251 MG, and HMC3 cells. We observed that fludarabine has shown cytotoxicity to these cells only at high doses indicating it could be safe for future clinical use if approved. In conclusion, this study suggests that fludarabine could be developed as a potential broad-spectrum anti-RNA virus therapeutic agent.

scholarly journals Essential role of IPS-1 in innate immune responses against RNA viruses

2006 ◽  
Vol 203 (7) ◽  
pp. 1795-1803 ◽  
Author(s):  
Himanshu Kumar ◽  
Taro Kawai ◽  
Hiroki Kato ◽  
Shintaro Sato ◽  
Ken Takahashi ◽  
...  
Keyword(s):  
Rna Viruses ◽  
Rna Virus ◽  
Critical Role ◽  
Nuclear Factor Κb ◽  
Type I ◽  
Innate Immune Responses ◽  
Antiviral Responses ◽  
Deficient Mice

IFN-β promoter stimulator (IPS)-1 was recently identified as an adapter for retinoic acid–inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (Mda5), which recognize distinct RNA viruses. Here we show the critical role of IPS-1 in antiviral responses in vivo. IPS-1–deficient mice showed severe defects in both RIG-I– and Mda5-mediated induction of type I interferon and inflammatory cytokines and were susceptible to RNA virus infection. RNA virus–induced interferon regulatory factor-3 and nuclear factor κB activation was also impaired in IPS-1–deficient cells. IPS-1, however, was not essential for the responses to either DNA virus or double-stranded B-DNA. Thus, IPS-1 is the sole adapter in both RIG-I and Mda5 signaling that mediates effective responses against a variety of RNA viruses.

scholarly journals Host-Pathogen Adhesion as the Basis of Innovative Diagnostics for Emerging Pathogens

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1259
Author(s):  
Alex van Belkum ◽  
Carina Almeida ◽  
Benjamin Bardiaux ◽  
Sarah V. Barrass ◽  
Sarah J. Butcher ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Receptor Binding ◽  
Pathogen Detection ◽  
Host Cells ◽  
Emerging Pathogens ◽  
Emerging Viruses ◽  
Ligand Interaction ◽  
Novel Structure ◽  
Specificity And Sensitivity

Infectious diseases are an existential health threat, potentiated by emerging and re-emerging viruses and increasing bacterial antibiotic resistance. Targeted treatment of infectious diseases requires precision diagnostics, especially in cases where broad-range therapeutics such as antibiotics fail. There is thus an increasing need for new approaches to develop sensitive and specific in vitro diagnostic (IVD) tests. Basic science and translational research are needed to identify key microbial molecules as diagnostic targets, to identify relevant host counterparts, and to use this knowledge in developing or improving IVD. In this regard, an overlooked feature is the capacity of pathogens to adhere specifically to host cells and tissues. The molecular entities relevant for pathogen–surface interaction are the so-called adhesins. Adhesins vary from protein compounds to (poly-)saccharides or lipid structures that interact with eukaryotic host cell matrix molecules and receptors. Such interactions co-define the specificity and sensitivity of a diagnostic test. Currently, adhesin-receptor binding is typically used in the pre-analytical phase of IVD tests, focusing on pathogen enrichment. Further exploration of adhesin–ligand interaction, supported by present high-throughput “omics” technologies, might stimulate a new generation of broadly applicable pathogen detection and characterization tools. This review describes recent results of novel structure-defining technologies allowing for detailed molecular analysis of adhesins, their receptors and complexes. Since the host ligands evolve slowly, the corresponding adhesin interaction is under selective pressure to maintain a constant receptor binding domain. IVD should exploit such conserved binding sites and, in particular, use the human ligand to enrich the pathogen. We provide an inventory of methods based on adhesion factors and pathogen attachment mechanisms, which can also be of relevance to currently emerging pathogens, including SARS-CoV-2, the causative agent of COVID-19.

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