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Virus Research Jan 2018Virus metagenomics is a young research filed but it has already transformed our understanding of virus diversity and evolution, and illuminated at a new level the... (Review)
Review
Virus metagenomics is a young research filed but it has already transformed our understanding of virus diversity and evolution, and illuminated at a new level the connections between virus evolution and the evolution and ecology of the hosts. In this review article, we examine the new picture of the evolution of RNA viruses, the dominant component of the eukaryotic virome, that is emerging from metagenomic data analysis. The major expansion of many groups of RNA viruses through metagenomics allowed the construction of substantially improved phylogenetic trees for the conserved virus genes, primarily, the RNA-dependent RNA polymerases (RdRp). In particular, a new superfamily of widespread, small positive-strand RNA viruses was delineated that unites tombus-like and noda-like viruses. Comparison of the genome architectures of RNA viruses discovered by metagenomics and by traditional methods reveals an extent of gene module shuffling among diverse virus genomes that far exceeds the previous appreciation of this evolutionary phenomenon. Most dramatically, inclusion of the metagenomic data in phylogenetic analyses of the RdRp resulted in the identification of numerous, strongly supported groups that encompass RNA viruses from diverse hosts including different groups of protists, animals and plants. Notwithstanding potential caveats, in particular, incomplete and uneven sampling of eukaryotic taxa, these highly unexpected findings reveal horizontal virus transfer (HVT) between diverse hosts as the central aspect of RNA virus evolution. The vast and diverse virome of invertebrates, particularly nematodes and arthropods, appears to be the reservoir, from which the viromes of plants and vertebrates evolved via multiple HVT events.
Topics: Animals; Arthropods; Disease Transmission, Infectious; Evolution, Molecular; Gene Expression; Genetic Variation; Genome, Viral; Metagenomics; Nematoda; Phylogeny; Plants; Prokaryotic Cells; RNA Viruses; RNA-Dependent RNA Polymerase; Vertebrates; Viral Proteins
PubMed: 29103997
DOI: 10.1016/j.virusres.2017.10.020 -
Current Opinion in Virology Dec 2011RNA viruses are notorious for rapidly generating genetically diverse populations during a single replication cycle, and the implications of this mutant population, often... (Review)
Review
RNA viruses are notorious for rapidly generating genetically diverse populations during a single replication cycle, and the implications of this mutant population, often referred to as quasispecies, can be vast. Previous studies have linked RNA virus genetic variability to changes in viral pathogenesis, the ability to adapt to a host during infection, and to the acquisition of mechanisms required to switch hosts entirely. However, these initial studies are just the beginning. With the development of next generation technologies, groups will be able to dig deeper into the sequence space that is generated during an RNA virus infection and more clearly understand the development, role, and consequences of viral genetic diversity.
Topics: Animals; DNA-Directed RNA Polymerases; Genetic Variation; Humans; Mutation; RNA Virus Infections; RNA Viruses; Virulence; Virus Replication
PubMed: 22440922
DOI: 10.1016/j.coviro.2011.09.012 -
The Journal of Physiology Jun 2024Information concepts from physics, mathematics and computer science support many areas of research in biology. Their focus is on objective information, which provides... (Review)
Review
Information concepts from physics, mathematics and computer science support many areas of research in biology. Their focus is on objective information, which provides correlations and patterns related to objects, processes, marks and signals. In these approaches only the quantitative aspects of the meaning of the information is relevant. In other areas of biology, 'meaningful information', which is subjective in nature, relies on the physiology of the organism's sensory organs and on the interpretation of the perceived signals, which is then translated into action, even if this is only mental (in brained animals). Information is involved, in terms of both amount and quality. Here we contextualize and review the main theories that deal with 'meaningful-information' at a molecular level from different areas of natural language research, namely biosemiotics, code-biology, biocommunication and biohermeneutics. As this information mediates between the organism and its environment, we emphasize how such theories compare with the neo-Darwinian treatment of genetic information, and how they project onto the rapid evolution of RNA viruses.
Topics: Animals; Humans; RNA Viruses; Evolution, Molecular
PubMed: 37983617
DOI: 10.1113/JP284415 -
Viruses Apr 2021RNA viruses cause a wide range of human diseases that are associated with high mortality and morbidity. In the past decades, the rise of genetic-based screening methods... (Review)
Review
RNA viruses cause a wide range of human diseases that are associated with high mortality and morbidity. In the past decades, the rise of genetic-based screening methods and high-throughput sequencing approaches allowed the uncovering of unique and elusive aspects of RNA virus replication and pathogenesis at an unprecedented scale. However, viruses often hijack critical host functions or trigger pathological dysfunctions, perturbing cellular proteostasis, macromolecular complex organization or stoichiometry, and post-translational modifications. Such effects require the monitoring of proteins and proteoforms both on a global scale and at the structural level. Mass spectrometry (MS) has recently emerged as an important component of the RNA virus biology toolbox, with its potential to shed light on critical aspects of virus-host perturbations and streamline the identification of antiviral targets. Moreover, multiple novel MS tools are available to study the structure of large protein complexes, providing detailed information on the exact stoichiometry of cellular and viral protein complexes and critical mechanistic insights into their functions. Here, we review top-down and bottom-up mass spectrometry-based approaches in RNA virus biology with a special focus on the most recent developments in characterizing host responses, and their translational implications to identify novel tractable antiviral targets.
Topics: Host Microbial Interactions; Humans; Proteomics; RNA Virus Infections; RNA Viruses; Tandem Mass Spectrometry; Virus Replication
PubMed: 33924391
DOI: 10.3390/v13040668 -
Advances in Virus Research 2022Reverse genetics is the prospective analysis of how genotype determines phenotype. In a typical experiment, a researcher alters a viral genome, then observes the...
Reverse genetics is the prospective analysis of how genotype determines phenotype. In a typical experiment, a researcher alters a viral genome, then observes the phenotypic outcome. Among RNA viruses, this approach was first applied to positive-strand RNA viruses in the mid-1970s and over nearly 50 years has become a powerful and widely used approach for dissecting the mechanisms of viral replication and pathogenesis. During this time the global health importance of two virus groups, flaviviruses (genus Flavivirus, family Flaviviridae) and betacoronaviruses (genus Betacoronavirus, subfamily Orthocoronavirinae, family Coronaviridae), have dramatically increased, yet these viruses have genomes that are technically challenging to manipulate. As a result, several new techniques have been developed to overcome these challenges. Here I briefly review key historical aspects of positive-strand RNA virus reverse genetics, describe some recent reverse genetic innovations, particularly as applied to flaviviruses and coronaviruses, and discuss their benefits and limitations within the larger context of rigorous genetic analysis.
Topics: Flavivirus; Genome, Viral; Positive-Strand RNA Viruses; RNA Viruses; Reverse Genetics; Virus Replication
PubMed: 35840179
DOI: 10.1016/bs.aivir.2022.03.001 -
Annual Review of Microbiology 1997RNA viruses exploit all known mechanisms of genetic variation to ensure their survival. Distinctive features of RNA virus replication include high mutation rates, high... (Review)
Review
RNA viruses exploit all known mechanisms of genetic variation to ensure their survival. Distinctive features of RNA virus replication include high mutation rates, high yields, and short replication times. As a consequence, RNA viruses replicate as complex and dynamic mutant swarms, called viral quasispecies. Mutation rates at defined genomic sites are affected by the nucleotide sequence context on the template molecule as well as by environmental factors. In vitro hypermutation reactions offer a means to explore the functional sequence space of nucleic acids and proteins. The evolution of a viral quasispecies is extremely dependent on the population size of the virus that is involved in the infections. Repeated bottleneck events lead to average fitness losses, with viruses that harbor unusual, deleterious mutations. In contrast, large population passages result in rapid fitness gains, much larger than those so far scored for cellular organisms. Fitness gains in one environment often lead to fitness losses in an alternative environment. An important challenge in RNA virus evolution research is the assignment of phenotypic traits to specific mutations. Different constellations of mutations may be associated with a similar biological behavior. In addition, recent evidence suggests the existence of critical thresholds for the expression of phenotypic traits. Epidemiological as well as functional and structural studies suggest that RNA viruses can tolerate restricted types and numbers of mutations during any specific time point during their evolution. Viruses occupy only a tiny portion of their potential sequence space. Such limited tolerance to mutations may open new avenues for combating viral infections.
Topics: Antiviral Agents; Biological Evolution; Gene Expression; Genome, Viral; Mutation; RNA Viruses; RNA, Viral; Recombination, Genetic; Virus Diseases; Virus Replication
PubMed: 9343347
DOI: 10.1146/annurev.micro.51.1.151 -
Viruses Aug 2022(HPgV-2) is a virus discovered in the plasma of a (HCV)-infected patient in 2015 belonging to the of the family . HPgV-2 has been proved to be epidemiologically... (Review)
Review
(HPgV-2) is a virus discovered in the plasma of a (HCV)-infected patient in 2015 belonging to the of the family . HPgV-2 has been proved to be epidemiologically associated with and structurally similar to HCV but unrelated to HCV disease and non-pathogenic, but its natural history and tissue tropism remain unclear. HPgV-2 is a unique RNA virus sharing the features of HCV and the first human pegivirus (HPgV-1 or GBV-C). Moreover, distinct from most RNA viruses such as HCV, HPgV-1 and human immunodeficiency virus (HIV), HPgV-2 exhibits much lower genomic diversity, with a high global sequence identity ranging from 93.5 to 97.5% and significantly lower intra-host variation than HCV. The mechanisms underlying the conservation of the HPgV-2 genome are not clear but may include efficient innate immune responses, low immune selection pressure and, possibly, the unique features of the viral RNA-dependent RNA polymerase (RdRP). In this review, we summarize the prevalence, pathogenicity and genetic diversity of HPgV-2 and discuss the possible reasons for the uniformity of its genome sequence, which should elucidate the implications of RNA virus fidelity for attenuated viral vaccines.
Topics: Flaviviridae; Flaviviridae Infections; Genetic Variation; Hepacivirus; Hepatitis C; Humans; Pegivirus; Phylogeny; Prevalence; RNA Viruses; RNA, Viral; RNA-Dependent RNA Polymerase; Viral Vaccines
PubMed: 36146649
DOI: 10.3390/v14091844 -
Journal of Invertebrate Pathology Jul 2017Invertebrates are hosts to diverse RNA viruses that have all possible types of encapsidated genomes (positive, negative and ambisense single stranded RNA genomes, or a... (Review)
Review
Invertebrates are hosts to diverse RNA viruses that have all possible types of encapsidated genomes (positive, negative and ambisense single stranded RNA genomes, or a double stranded RNA genome). These viruses also differ markedly in virion morphology and genome structure. Invertebrate RNA viruses are present in three out of four currently recognized orders of RNA viruses: Mononegavirales, Nidovirales, and Picornavirales, and 10 out of 37 RNA virus families that have yet to be assigned to an order. This mini-review describes general properties of the taxonomic groups, which include invertebrate RNA viruses on the basis of their current classification by the International Committee on Taxonomy of Viruses (ICTV).
Topics: Animals; Host-Pathogen Interactions; Invertebrates; Mononegavirales; Nidovirales; Phylogeny; Picornaviridae
PubMed: 27793741
DOI: 10.1016/j.jip.2016.10.002 -
Current Topics in Microbiology and... 1992RNA virus mutation frequencies generally approach maximum tolerable levels, and create complex indeterminate quasispecies populations in infected hosts. This usually... (Review)
Review
RNA virus mutation frequencies generally approach maximum tolerable levels, and create complex indeterminate quasispecies populations in infected hosts. This usually favors extreme rates of evolution, although periods of relative stasis or equilibrium, punctuated by rapid change may also occur (as for other life forms). Because complex quasispecies populations of RNA viruses arise probabilistically and differentially in every host, their compositions and exact roles in disease pathogenesis are indeterminate and their directions of evolution, and the nature and timing of "new" virus outbreaks are unpredictable.
Topics: Biological Evolution; Humans; Mutation; RNA Viruses; Species Specificity; Virus Diseases
PubMed: 1600747
DOI: 10.1007/978-3-642-77011-1_1 -
Scientific Reports Mar 2021The replication machinery of most RNA viruses lacks proofreading mechanisms. As a result, RNA virus populations harbor a large amount of genetic diversity that confers...
The replication machinery of most RNA viruses lacks proofreading mechanisms. As a result, RNA virus populations harbor a large amount of genetic diversity that confers them the ability to rapidly adapt to changes in their environment. In this work, we investigate whether further increasing the initial population diversity of a model RNA virus can improve adaptation to a single selection pressure, thermal inactivation. For this, we experimentally increased the diversity of coxsackievirus B3 (CVB3) populations across the capsid region. We then compared the ability of these high diversity CVB3 populations to achieve resistance to thermal inactivation relative to standard CVB3 populations in an experimental evolution setting. We find that viral populations with high diversity are better able to achieve resistance to thermal inactivation at both the temperature employed during experimental evolution as well as at a more extreme temperature. Moreover, we identify mutations in the CVB3 capsid that confer resistance to thermal inactivation, finding significant mutational epistasis. Our results indicate that even naturally diverse RNA virus populations can benefit from experimental augmentation of population diversity for optimal adaptation and support the use of such viral populations in directed evolution efforts that aim to select viruses with desired characteristics.
Topics: Amino Acid Substitution; Biodiversity; Biological Evolution; Capsid; Capsid Proteins; Cell Line; Computational Biology; Genetic Variation; Humans; Mutation; RNA Viruses
PubMed: 33767337
DOI: 10.1038/s41598-021-86375-z