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Viruses Feb 2021RNA viruses are the fastest evolving known biological entities. Consequently, the sequence similarity between homologous viral proteins disappears quickly, limiting the...
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.
Topics: Models, Molecular; Phylogeny; Protein Conformation, alpha-Helical; Protein Domains; RNA Viruses; RNA-Dependent RNA Polymerase; Viral Proteins
PubMed: 33671332
DOI: 10.3390/v13020313 -
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 -
Expert Review of Vaccines Sep 2016A novel vaccine platform uses DNA immunization to launch live-attenuated virus vaccines in vivo. This technology has been applied for vaccine development against... (Review)
Review
A novel vaccine platform uses DNA immunization to launch live-attenuated virus vaccines in vivo. This technology has been applied for vaccine development against positive-strand RNA viruses with global public health impact including alphaviruses and flaviviruses. The DNA-launched vaccine represents the recombinant plasmid that encodes the full-length genomic RNA of live-attenuated virus downstream from a eukaryotic promoter. When administered in vivo, the genomic RNA of live-attenuated virus is transcribed. The RNA initiates limited replication of a genetically defined, live-attenuated vaccine virus in the tissues of the vaccine recipient, thereby inducing a protective immune response. This platform combines the strengths of reverse genetics, DNA immunization and the advantages of live-attenuated vaccines, resulting in a reduced chance of genetic reversions, increased safety, and improved immunization. With this vaccine technology, the field of DNA vaccines is expanded from those that express subunit antigens to include a novel type of DNA vaccines that launch live-attenuated viruses.
Topics: Animals; Humans; Plasmids; RNA Virus Infections; RNA Viruses; RNA, Viral; Vaccines, Attenuated; Vaccines, DNA; Viral Vaccines
PubMed: 27055100
DOI: 10.1080/14760584.2016.1175943 -
Biochimica Et Biophysica Acta. General... Mar 2021Mitochondria are multi-functioning organelles that participate in a wide range of biologic processes from energy metabolism to cellular suicide. Mitochondria are also... (Review)
Review
Mitochondria are multi-functioning organelles that participate in a wide range of biologic processes from energy metabolism to cellular suicide. Mitochondria are also involved in the cellular innate immune response against microorganisms or environmental irritants, particularly in mammals. Mitochondrial-mediated innate immunity is achieved by the activation of two discrete signaling pathways, the NLR family pyrin domain-containing 3 inflammasomes and the retinoic acid-inducible gene I-like receptor pathway. In both pathways, a mitochondrial outer membrane adaptor protein, called mitochondrial antiviral signaling MAVS, and mitochondria-derived components play a key role in signal transduction. In this review, we discuss current insights regarding the fundamental phenomena of mitochondrial-related innate immune responses, and review the specific roles of various mitochondrial subcompartments in fine-tuning innate immune signaling events. We propose that specific targeting of mitochondrial functions is a potential therapeutic approach for the management of infectious diseases and autoinflammatory disorders with an excessive immune response.
Topics: Adaptor Proteins, Signal Transducing; Animals; DEAD Box Protein 58; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Immunity, Innate; Inflammasomes; MicroRNAs; Mitochondria; Mitochondrial Membranes; NLR Family, Pyrin Domain-Containing 3 Protein; RNA Virus Infections; RNA Viruses; Receptors, Immunologic; Signal Transduction
PubMed: 33412226
DOI: 10.1016/j.bbagen.2020.129839 -
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 -
Viruses Feb 2021The RNA helicase A (RHA) is a member of DExH-box helicases and characterized by two double-stranded RNA binding domains at the N-terminus. RHA unwinds double-stranded... (Review)
Review
The RNA helicase A (RHA) is a member of DExH-box helicases and characterized by two double-stranded RNA binding domains at the N-terminus. RHA unwinds double-stranded RNA in vitro and is involved in RNA metabolisms in the cell. RHA is also hijacked by a variety of RNA viruses to facilitate virus replication. Herein, this review will provide an overview of the role of RHA in the replication of RNA viruses.
Topics: Animals; DEAD-box RNA Helicases; Humans; RNA Helicases; RNA Viruses; RNA, Double-Stranded; RNA, Viral; Virus Replication
PubMed: 33668948
DOI: 10.3390/v13030361 -
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