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Microbes and Environments 2022Isolated RNA viruses mainly parasitize eukaryotes. RNA viruses either expand horizontally by infecting hosts (acute type) or coexist with the host and are vertically... (Review)
Review
Isolated RNA viruses mainly parasitize eukaryotes. RNA viruses either expand horizontally by infecting hosts (acute type) or coexist with the host and are vertically inherited (persistent type). The significance of persistent-type RNA viruses in environmental viromes (the main hosts are expected to be microbes) was only recently reported because they had previously been overlooked in virology. In this review, we summarize the host-virus relationships of eukaryotic microbial RNA viruses. Picornavirales and Reoviridae are recognized as representative acute-type virus families, and most of the microbial viruses in Narnaviridae, Totiviridae, and Partitiviridae are categorized as representative persistent-type viruses. Acute-type viruses have only been found in aquatic environments, while persistent-type viruses are present in various environments, including aquatic environments. Moreover, persistent-type viruses are potentially widely spread in the RNA viral sequence space. This emerging evidence provides novel insights into RNA viral diversity, host-virus relationships, and their history of co-evolution.
Topics: Ecosystem; Eukaryota; Genome, Viral; RNA; RNA Viruses; Viruses
PubMed: 35922920
DOI: 10.1264/jsme2.ME22034 -
Trends in Plant Science Jan 2006Recessive resistance genes against plant viruses have been recognized for a long time but their molecular nature has only recently been linked to components of the... (Review)
Review
Recessive resistance genes against plant viruses have been recognized for a long time but their molecular nature has only recently been linked to components of the eukaryotic translation initiation complex. Translation initiation factors, and particularly the eIF4E and eIF4G protein families, were found to be essential determinants in the outcome of RNA virus infections. Viruses affected by these genes belong mainly to potyviruses; natural viral resistance mechanisms as well as mutagenesis analysis in Arabidopsis all converged to identify the same set of translation initiation factors. Their role in plant resistance against RNA viruses remains to be elucidated. Although the interaction with the protein synthesis machinery is probably a key element for successful RNA virus infection, other possible mechanisms will also be discussed.
Topics: Eukaryotic Initiation Factors; Plant Diseases; Plant Viruses; Plants; Protein Biosynthesis; RNA Viruses
PubMed: 16343979
DOI: 10.1016/j.tplants.2005.11.004 -
Genome Biology and Evolution Feb 2018Many viroids and RNA viruses have genomes that exhibit secondary structure, with paired nucleotides forming stems and loops. Such structures violate a key assumption of...
Many viroids and RNA viruses have genomes that exhibit secondary structure, with paired nucleotides forming stems and loops. Such structures violate a key assumption of most methods of phylogenetic reconstruction, that sequence change is independent among sites. However, phylogenetic analyses of these transmissible agents rarely use evolutionary models that account for RNA secondary structure. Here, we assess the effect of using RNA-specific nucleotide substitution models on the phylogenetic inference of viroids and RNA viruses. We obtained data sets comprising full-genome nucleotide sequences from six viroid and ten single-stranded RNA virus species. For each alignment, we inferred consensus RNA secondary structures, then evaluated different DNA and RNA substitution models. We used model selection to choose the best-fitting model and evaluate estimated Bayesian phylogenies. Further, for each data set we generated and compared Robinson-Foulds (RF) statistics in order to test whether the distributions of trees generated under alternative models are notably different to each other. In all alignments, the best-fitting model was one that considers RNA secondary structure: RNA models that allow a nonzero rate of double substitution (RNA16A and RNA16C) fitted best for both viral and viroid data sets. In 14 of 16 data sets, the use of an RNA-specific model led to significantly longer tree lengths, but only in three cases did it have a significant effect on RFs. In conclusion, using RNA model when undertaking phylogenetic inference of viroids and RNA viruses can provide a better model fit than standard approaches and model choice can significantly affect branch length estimates.
Topics: Models, Genetic; Phylogeny; RNA Viruses; Viroids
PubMed: 29325030
DOI: 10.1093/gbe/evx273 -
Molecules (Basel, Switzerland) Dec 2018Self-replicating single-stranded RNA viruses such as alphaviruses, flaviviruses, measles viruses, and rhabdoviruses provide efficient delivery and high-level expression... (Review)
Review
Self-replicating single-stranded RNA viruses such as alphaviruses, flaviviruses, measles viruses, and rhabdoviruses provide efficient delivery and high-level expression of therapeutic genes due to their high capacity of RNA replication. This has contributed to novel approaches for therapeutic applications including vaccine development and gene therapy-based immunotherapy. Numerous studies in animal tumor models have demonstrated that self-replicating RNA viral vectors can generate antibody responses against infectious agents and tumor cells. Moreover, protection against challenges with pathogenic Ebola virus was obtained in primates immunized with alphaviruses and flaviviruses. Similarly, vaccinated animals have been demonstrated to withstand challenges with lethal doses of tumor cells. Furthermore, clinical trials have been conducted for several indications with self-amplifying RNA viruses. In this context, alphaviruses have been subjected to phase I clinical trials for a cytomegalovirus vaccine generating neutralizing antibodies in healthy volunteers, and for antigen delivery to dendritic cells providing clinically relevant antibody responses in cancer patients, respectively. Likewise, rhabdovirus particles have been subjected to phase I/II clinical trials showing good safety and immunogenicity against Ebola virus. Rhabdoviruses have generated promising results in phase III trials against Ebola virus. The purpose of this review is to summarize the achievements of using self-replicating RNA viruses for RNA therapy based on preclinical animal studies and clinical trials in humans.
Topics: Animals; Clinical Trials as Topic; Humans; RNA; RNA Viruses; Virus Replication
PubMed: 30551668
DOI: 10.3390/molecules23123310 -
Proceedings of the National Academy of... Jun 2001RNA viruses evolve rapidly. One source of this ability to rapidly change is the apparently high mutation frequency in RNA virus populations. A high mutation frequency is...
RNA viruses evolve rapidly. One source of this ability to rapidly change is the apparently high mutation frequency in RNA virus populations. A high mutation frequency is a central tenet of the quasispecies theory. A corollary of the quasispecies theory postulates that, given their high mutation frequency, animal RNA viruses may be susceptible to error catastrophe, where they undergo a sharp drop in viability after a modest increase in mutation frequency. We recently showed that the important broad-spectrum antiviral drug ribavirin (currently used to treat hepatitis C virus infections, among others) is an RNA virus mutagen, and we proposed that ribavirin's antiviral effect is by forcing RNA viruses into error catastrophe. However, a direct demonstration of error catastrophe has not been made for ribavirin or any RNA virus mutagen. Here we describe a direct demonstration of error catastrophe by using ribavirin as the mutagen and poliovirus as a model RNA virus. We demonstrate that ribavirin's antiviral activity is exerted directly through lethal mutagenesis of the viral genetic material. A 99.3% loss in viral genome infectivity is observed after a single round of virus infection in ribavirin concentrations sufficient to cause a 9.7-fold increase in mutagenesis. Compiling data on both the mutation levels and the specific infectivities of poliovirus genomes produced in the presence of ribavirin, we have constructed a graph of error catastrophe showing that normal poliovirus indeed exists at the edge of viability. These data suggest that RNA virus mutagens may represent a promising new class of antiviral drugs.
Topics: Antiviral Agents; Base Sequence; HeLa Cells; Humans; Molecular Sequence Data; Mutation; Poliovirus; RNA Viruses; Ribavirin; Virus Replication
PubMed: 11371613
DOI: 10.1073/pnas.111085598 -
Nucleic Acids Research Jan 2009The RNA Virus Database is a database and web application describing the genome organization and providing analytical tools for the 938 known species of RNA virus. It can...
The RNA Virus Database is a database and web application describing the genome organization and providing analytical tools for the 938 known species of RNA virus. It can identify submitted nucleotide sequences, can place them into multiple whole-genome alignments (in species where more than one isolate has been fully sequenced) and contains translated genome sequences for all species. It has been created for two main purposes: to facilitate the comparative analysis of RNA viruses and to become a hub for other, more specialised virus Web sites. It is available at the following four mirrored sites. http://virus.zoo.ox.ac.uk/rnavirusdb; http://hivweb.sanbi.ac.za/rnavirusdb; http://bioinf.cs.auckland.ac.nz/rnavirusdb; http://tree.bio.ed.ac.uk/rnavirusdb.
Topics: Base Sequence; Databases, Nucleic Acid; Genes, Viral; Genome, Viral; Genomics; RNA Viruses; Sequence Alignment
PubMed: 18948277
DOI: 10.1093/nar/gkn729 -
Viruses Sep 2021To generate infectious viral particles, viruses must specifically select their genomic RNA from milieu that contains a complex mixture of cellular or non-genomic viral... (Review)
Review
To generate infectious viral particles, viruses must specifically select their genomic RNA from milieu that contains a complex mixture of cellular or non-genomic viral RNAs. In this review, we focus on the role of viral encoded RNA structures in genome packaging. We first discuss how packaging signals are constructed from local and long-range base pairings within viral genomes, as well as inter-molecular interactions between viral and host RNAs. Then, how genome packaging is regulated by the biophysical properties of RNA. Finally, we examine the impact of RNA packaging signals on viral evolution.
Topics: Evolution, Molecular; Genome, Viral; Humans; Nucleic Acid Conformation; RNA Viruses; RNA, Viral; Virus Assembly
PubMed: 34578369
DOI: 10.3390/v13091788 -
Protein & Cell Dec 2012Nucleocapsid protein (NPs) of negative-sense single-stranded RNA (-ssRNA) viruses function in different stages of viral replication, transcription, and maturation.... (Review)
Review
Nucleocapsid protein (NPs) of negative-sense single-stranded RNA (-ssRNA) viruses function in different stages of viral replication, transcription, and maturation. Structural investigations show that -ssRNA viruses that encode NPs preliminarily serve as structural building blocks that encapsidate and protect the viral genomic RNA and mediate the interaction between genomic RNA and RNA-dependent RNA polymerase. However, recent structural results have revealed other biological functions of -ssRNA viruses that extend our understanding of the versatile roles of virally encoded NPs.
Topics: Animals; Capsid; Humans; Lassa virus; Nucleocapsid Proteins; Orthobunyavirus; RNA Viruses
PubMed: 23136065
DOI: 10.1007/s13238-012-2087-5 -
Journal of Virology Apr 2003
Review
Topics: Animals; Evolution, Molecular; Humans; Models, Genetic; Phylogeny; RNA Viruses; Time Factors
PubMed: 12634349
DOI: 10.1128/jvi.77.7.3893-3897.2003 -
Nature Reviews. Microbiology Jul 2016Segmented RNA viruses are widespread in nature and include important human, animal and plant pathogens, such as influenza viruses and rotaviruses. Although the origin of... (Review)
Review
Segmented RNA viruses are widespread in nature and include important human, animal and plant pathogens, such as influenza viruses and rotaviruses. Although the origin of RNA virus genome segmentation remains elusive, a major consequence of this genome structure is the capacity for reassortment to occur during co-infection, whereby segments are exchanged among different viral strains. Therefore, reassortment can create viral progeny that contain genes that are derived from more than one parent, potentially conferring important fitness advantages or disadvantages to the progeny virus. However, for segmented RNA viruses that package their multiple genome segments into a single virion particle, reassortment also requires genetic compatibility between parental strains, which occurs in the form of conserved packaging signals, and the maintenance of RNA and protein interactions. In this Review, we discuss recent studies that examined the mechanisms and outcomes of reassortment for three well-studied viral families - Cystoviridae, Orthomyxoviridae and Reoviridae - and discuss how these findings provide new perspectives on the replication and evolution of segmented RNA viruses.
Topics: Animals; Cystoviridae; Evolution, Molecular; Genome, Viral; Humans; Influenza A virus; Orthomyxoviridae; RNA Viruses; RNA, Viral; Reassortant Viruses; Recombination, Genetic; Reoviridae; Virus Replication
PubMed: 27211789
DOI: 10.1038/nrmicro.2016.46