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Microbes and Infection Nov 2002The antiviral drug ribavirin exhibits strong antiviral activity against a broad range of RNA viruses. This drug is currently used clinically to treat hepatitis C virus... (Review)
Review
The antiviral drug ribavirin exhibits strong antiviral activity against a broad range of RNA viruses. This drug is currently used clinically to treat hepatitis C virus infections, respiratory syncytial virus infections, and Lassa fever virus infections. Although ribavirin was discovered in 1972, its mechanism of action has remained unclear until recently. Using poliovirus as an RNA virus model, it was shown that ribavirin is a virus mutagen, and it was proposed that the primary mechanism of action of ribavirin is via lethal mutagenesis of the RNA virus genomes. This represents a novel antiviral mechanism of action and provides a model for the development of new antiviral strategies. In this review we discuss the genetic explanations, evolutionary implications, and drug development opportunities associated with RNA virus mutagenesis.
Topics: Antiviral Agents; Drug Design; Genes, Lethal; Models, Molecular; Mutagenesis; Mutation; Poliovirus; RNA Viruses; Ribavirin
PubMed: 12443894
DOI: 10.1016/s1286-4579(02)00008-4 -
Frontiers in Cellular and Infection... 2023While the function of cGAS/STING signalling axis in the innate immune response to DNA viruses is well deciphered, increasing evidence demonstrates its significant... (Review)
Review
While the function of cGAS/STING signalling axis in the innate immune response to DNA viruses is well deciphered, increasing evidence demonstrates its significant contribution in the control of RNA virus infections. After the first evidence of cGAS/STING antagonism by flaviviruses, STING activation has been detected following infection by various enveloped RNA viruses. It has been discovered that numerous viral families have implemented advanced strategies to antagonize STING pathway through their evolutionary path. This review summarizes the characterized cGAS/STING escape strategies to date, together with the proposed mechanisms of STING signalling activation perpetrated by RNA viruses and discusses possible therapeutic approaches. Further studies regarding the interaction between RNA viruses and cGAS/STING-mediated immunity could lead to major discoveries important for the understanding of immunopathogenesis and for the treatment of RNA viral infections.
Topics: Humans; Immunity, Innate; Nucleotidyltransferases; RNA Viruses; Signal Transduction
PubMed: 37077526
DOI: 10.3389/fcimb.2023.1172739 -
MBio Oct 2022RNA viruses include respiratory viruses, such as coronaviruses and influenza viruses, as well as vector-borne viruses, like dengue and West Nile virus. RNA viruses like... (Review)
Review
RNA viruses include respiratory viruses, such as coronaviruses and influenza viruses, as well as vector-borne viruses, like dengue and West Nile virus. RNA viruses like these encounter various environments when they copy themselves and spread from cell to cell or host to host. differences, such as geographical location and humidity, affect their stability and transmission, while differences, such as pH and host gene expression, impact viral receptor binding, viral replication, and the host immune response against the viral infection. A critical factor affecting RNA viruses both and , and defining the outcome of viral infections and the direction of viral evolution, is temperature. In this minireview, we discuss the impact of temperature on viral replication, stability, transmission, and adaptation, as well as the host innate immune response. Improving our understanding of how RNA viruses function, survive, and spread at different temperatures will improve our models of viral replication and transmission risk analyses.
Topics: Humans; Temperature; Virus Replication; RNA Viruses; West Nile virus; RNA Virus Infections
PubMed: 35980031
DOI: 10.1128/mbio.02021-22 -
Virus Research Jan 2018Metagenomics is transforming the study of virus evolution, allowing the full assemblage of virus genomes within a host sample to be determined rapidly and cheaply. The... (Review)
Review
Metagenomics is transforming the study of virus evolution, allowing the full assemblage of virus genomes within a host sample to be determined rapidly and cheaply. The genomic analysis of complete transcriptomes, so-called meta-transcriptomics, is providing a particularly rich source of data on the global diversity of RNA viruses and their evolutionary history. Herein we review some of the insights that meta-transcriptomics has provided on the fundamental patterns and processes of virus evolution, with a focus on the recent discovery of a multitude of novel invertebrate viruses. In particular, meta-transcriptomics shows that the RNA virus world is more fluid than previously realized, with relatively frequent changes in genome length and structure. As well as having a transformative impact on studies of virus evolution, meta-transcriptomics presents major new challenges for virus classification, with the greater sampling of host taxa now filling many of the gaps on virus phylogenies that were previously used to define taxonomic groups. Given that most viruses in the future will likely be characterized using metagenomics approaches, and that we have evidently only sampled a tiny fraction of the total virosphere, we suggest that proposals for virus classification pay careful attention to the wonders unearthed in this new age of virus discovery.
Topics: Animals; Evolution, Molecular; Genome, Viral; Humans; Metagenomics; Phylogeny; RNA Virus Infections; RNA Viruses
PubMed: 29111455
DOI: 10.1016/j.virusres.2017.10.016 -
Viruses Feb 2021Recent research indicates that most tissue and cell types can secrete and release membrane-enclosed small vesicles, known as exosomes, whose content reflects the... (Review)
Review
Recent research indicates that most tissue and cell types can secrete and release membrane-enclosed small vesicles, known as exosomes, whose content reflects the physiological/pathological state of the cells from which they originate. These exosomes participate in the communication and cell-to-cell transfer of biologically active proteins, lipids, and nucleic acids. Studies of RNA viruses have demonstrated that exosomes release regulatory factors from infected cells and deliver other functional host genetic elements to neighboring cells, and these functions are involved in the infection process and modulate the cellular responses. This review provides an overview of the biogenesis, composition, and some of the most striking functions of exosome secretion and identifies physiological/pathological areas in need of further research. While initial indications suggest that exosome-mediated pathways operate in vivo, the exosome mechanisms involved in the related effects still need to be clarified. The current review focuses on the role of exosomes in RNA virus infections, with an emphasis on the potential contributions of exosomes to pathogenesis.
Topics: Exosomes; Organelle Biogenesis; RNA Virus Infections; RNA Viruses; Virus Replication
PubMed: 33567490
DOI: 10.3390/v13020256 -
Current Opinion in Virology Apr 2017Chronic disease associated with persistent RNA virus infections represents a key public health concern. While human immunodeficiency virus-1 and hepatitis C virus are... (Review)
Review
Chronic disease associated with persistent RNA virus infections represents a key public health concern. While human immunodeficiency virus-1 and hepatitis C virus are perhaps the most well-known examples of persistent RNA viruses that cause chronic disease, evidence suggests that many other RNA viruses, including re-emerging viruses such as chikungunya virus, Ebola virus and Zika virus, establish persistent infections. The mechanisms by which RNA viruses drive chronic disease are poorly understood. Here, we discuss how the persistence of viral RNA may drive chronic disease manifestations via the activation of RNA sensing pathways.
Topics: Chronic Disease; Host-Pathogen Interactions; Humans; Pathogen-Associated Molecular Pattern Molecules; RNA Virus Infections; RNA Viruses
PubMed: 28214732
DOI: 10.1016/j.coviro.2017.01.003 -
Proceedings of the National Academy of... Aug 2014Mycoviruses are widespread in nature and often occur with dsRNA and positive-stranded RNA genomes. Recently, strong evidence from RNA sequencing analysis suggested that...
Mycoviruses are widespread in nature and often occur with dsRNA and positive-stranded RNA genomes. Recently, strong evidence from RNA sequencing analysis suggested that negative-stranded (-)ssRNA viruses could infect fungi. Here we describe a (-)ssRNA virus, Sclerotinia sclerotiorum negative-stranded RNA virus 1 (SsNSRV-1), isolated from a hypovirulent strain of Sclerotinia sclerotiorum. The complete genome of SsNSRV-1 is 10,002 nt with six ORFs that are nonoverlapping and linearly arranged. Conserved gene-junction sequences that occur widely in mononegaviruses, (A/U)(U/A/C)UAUU(U/A)AA(U/G)AAAACUUAGG(A/U)(G/U), were identified between these ORFs. The analyses 5' and 3' rapid amplification of cDNA ends showed that all genes can be transcribed independently. ORF V encodes the largest protein that contains a conserved mononegaviral RNA-dependent RNA polymerase (RdRp) domain. Putative enveloped virion-like structures with filamentous morphology similar to members of Filoviridae were observed both in virion preparation samples and in ultrathin hyphal sections. The nucleocapsids are long, flexible, and helical; and are 22 nm in diameter and 200-2,000 nm in length. SDS/PAGE showed that the nucleocapsid possibly contains two nucleoproteins with different molecular masses, ∼43 kDa (p43) and ∼41 kDa (p41), and both are translated from ORF II. Purified SsNSRV-1 virions successfully transfected a virus-free strain of S. sclerotiorum and conferred hypovirulence. Phylogenetic analysis based on RdRp showed that SsNSRV-1 is clustered with viruses of Nyamiviridae and Bornaviridae. Moreover, SsNSRV-1 is widely distributed, as it has been detected in different regions of China. Our findings demonstrate that a (-)ssRNA virus can occur naturally in fungi and enhance our understanding of the ecology and evolution of (-)ssRNA viruses.
Topics: Amino Acid Sequence; Bornaviridae; Bunyaviridae; Electrophoresis, Polyacrylamide Gel; Fungi; Molecular Sequence Data; Phylogeny; RNA Viruses; Sequence Homology, Amino Acid; Viral Proteins
PubMed: 25092337
DOI: 10.1073/pnas.1401786111 -
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 -
Molecular Biology and Evolution Jan 2021RNA viruses are responsible for some of the worst pandemics known to mankind, including outbreaks of Influenza, Ebola, and COVID-19. One major challenge in tackling RNA...
RNA viruses are responsible for some of the worst pandemics known to mankind, including outbreaks of Influenza, Ebola, and COVID-19. One major challenge in tackling RNA viruses is the fact they are extremely genetically diverse. Nevertheless, they share common features that include their dependence on host cells for replication, and high mutation rates. We set out to search for shared evolutionary characteristics that may aid in gaining a broader understanding of RNA virus evolution, and constructed a phylogeny-based data set spanning thousands of sequences from diverse single-stranded RNA viruses of animals. Strikingly, we found that the vast majority of these viruses have a skewed nucleotide composition, manifested as adenine rich (A-rich) coding sequences. In order to test whether A-richness is driven by selection or by biased mutation processes, we harnessed the effects of incomplete purifying selection at the tips of virus phylogenies. Our results revealed consistent mutational biases toward U rather than A in genomes of all viruses. In +ssRNA viruses, we found that this bias is compensated by selection against U and selection for A, which leads to A-rich genomes. In -ssRNA viruses, the genomic mutational bias toward U on the negative strand manifests as A-rich coding sequences, on the positive strand. We investigated possible reasons for the advantage of A-rich sequences including weakened RNA secondary structures, codon usage bias, and selection for a particular amino acid composition, and conclude that host immune pressures may have led to similar biases in coding sequence composition across very divergent RNA viruses.
Topics: Animals; Codon; DNA Mutational Analysis; Databases, Factual; Evolution, Molecular; Genome, Viral; Humans; Mutation; Nucleotides; Phylogeny; RNA Viruses; RNA, Viral; SARS-CoV-2; Selection, Genetic
PubMed: 32986832
DOI: 10.1093/molbev/msaa247 -
Virus Research Jan 2018It is hard to overemphasize the role that metagenomics has had on our recent understanding of RNA virus diversity. Metagenomics in the 21st century has brought with it... (Review)
Review
It is hard to overemphasize the role that metagenomics has had on our recent understanding of RNA virus diversity. Metagenomics in the 21st century has brought with it an explosion in the number of RNA virus species, genera, and families far exceeding that following the discovery of the microscope in the 18th century for eukaryotic life or culture media in the 19th century for bacteriology or the 20th century for virology. When the definition of success in organism discovery is measured by sequence diversity and evolutionary distance, RNA viruses win. This review explores the history of RNA virus metagenomics, reasons for the successes so far in RNA virus metagenomics, and methodological concerns. In addition, the review briefly covers clinical metagenomics and environmental metagenomics and highlights some of the critical accomplishments that have defined the fast pace of RNA virus discoveries in recent years. Slightly more than a decade in, the field is exhausted from its discoveries but knows that there is yet even more out there to be found.
Topics: Animals; Bibliometrics; Biological Evolution; Genetic Variation; Humans; Metagenomics; Molecular Typing; Phylogeny; Plants; Prokaryotic Cells; RNA Viruses; Terminology as Topic; Virus Diseases
PubMed: 29055712
DOI: 10.1016/j.virusres.2017.10.014