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Computers in Biology and Medicine Feb 2024RNA viruses are major human pathogens that cause seasonal epidemics and occasional pandemic outbreaks. Due to the nature of their RNA genomes, it is anticipated that...
RNA viruses are major human pathogens that cause seasonal epidemics and occasional pandemic outbreaks. Due to the nature of their RNA genomes, it is anticipated that virus's RNA interacts with host protein (INTPRO), messenger RNA (INTmRNA), and non-coding RNA (INTncRNA) to perform their particular functions during their transcription and replication. In other words, thus, it is urgently needed to have such valuable data on virus RNA-directed molecular interactions (especially INTPROs), which are highly anticipated to attract broad research interests in the fields of RNA virus translation and replication. In this study, a new database was constructed to describe the virus RNA-directed interaction (INTPRO, INTmRNA, INTncRNA) for RNA virus (RVvictor). This database is unique in a) unambiguously characterizing the interactions between viruses RNAs and host proteins, b) providing, for the first time, the most systematic RNA-directed interaction data resources in providing clues to understand the molecular mechanisms of RNA viruses' translation, and replication, and c) in RVvictor, comprehensive enrichment analysis is conducted for each virus RNA based on its associated target genes/proteins, and the enrichment results were explicitly illustrated using various graphs. We found significant enrichment of a suite of pathways related to infection, translation, and replication, e.g., HIV infection, coronavirus disease, regulation of viral genome replication, and so on. Due to the devastating and persistent threat posed by the RNA virus, RVvictor constructed, for the first time, a possible network of cross-talk in RNA-directed interaction, which may ultimately explain the pathogenicity of RNA virus infection. The knowledge base might help develop new anti-viral therapeutic targets in the future. It's now free and publicly accessible at: https://idrblab.org/rvvictor/.
Topics: Humans; HIV Infections; RNA, Viral; RNA Viruses; Virus Replication; Gene Expression Regulation
PubMed: 38157777
DOI: 10.1016/j.compbiomed.2023.107886 -
Antiviral Chemistry & Chemotherapy 2020Zoonotic spillover, i.e. pathogen transmission from animal to human, has repeatedly introduced RNA viruses into the human population. In some cases, where these viruses... (Review)
Review
Zoonotic spillover, i.e. pathogen transmission from animal to human, has repeatedly introduced RNA viruses into the human population. In some cases, where these viruses were then efficiently transmitted between humans, they caused large disease outbreaks such as the 1918 flu pandemic or, more recently, outbreaks of Ebola and Coronavirus disease. These examples demonstrate that RNA viruses pose an immense burden on individual and public health with outbreaks threatening the economy and social cohesion within and across borders. And while emerging RNA viruses are introduced more frequently as human activities increasingly disrupt wild-life eco-systems, therapeutic or preventative medicines satisfying the "one drug-multiple bugs"-aim are unavailable. As one central aspect of preparedness efforts, this review digs into the development of broadly acting antivirals targeting viral genome synthesis with host- or virus-directed drugs centering around nucleotides, the genomes' universal building blocks. Following the first strategy, selected examples of host nucleotide synthesis inhibitors are presented that ultimately interfere with viral nucleic acid synthesis, with ribavirin being the most prominent and widely used example. For directly targeting the viral polymerase, nucleoside and nucleotide analogues (NNAs) have long been at the core of antiviral drug development and this review illustrates different molecular strategies by which NNAs inhibit viral infection. Highlighting well-known as well as recent, clinically promising compounds, structural features and mechanistic details that may confer broad-spectrum activity are discussed. The final part addresses limitations of NNAs for clinical development such as low efficacy or mitochondrial toxicity and illustrates strategies to overcome these.
Topics: Animals; Antiviral Agents; Genome, Viral; Humans; RNA Virus Infections; RNA Viruses
PubMed: 33297724
DOI: 10.1177/2040206620976786 -
Current Opinion in Virology Oct 2012In general terms, robustness is the capacity of biological systems to function in spite of genetic or environmental perturbations. The small and compacted genomes and... (Review)
Review
In general terms, robustness is the capacity of biological systems to function in spite of genetic or environmental perturbations. The small and compacted genomes and high mutation rates of RNA viruses, as well as the ever-changing environments wherein they replicate, create the conditions for robustness to be advantageous. In this review, I will enumerate possible mechanisms by which viral populations may acquire robustness, distinguishing between mechanisms that are inherent to virus replication and population dynamics and those that result from the interaction with host factors. Then, I will move to review some evidences that RNA virus populations are robust indeed. Finally, I will comment on the implications of robustness for virus evolvability, the emergence of new viruses and the efficiency of lethal mutagenesis as an antiviral strategy.
Topics: Animals; Evolution, Molecular; Humans; RNA Virus Infections; RNA Viruses; Virus Replication
PubMed: 22818515
DOI: 10.1016/j.coviro.2012.06.008 -
Virus Research Apr 2021The negative strand RNA virus family contains many human pathogens. Finding new antiviral drug targets against this class of human pathogens is one of the significant...
The negative strand RNA virus family contains many human pathogens. Finding new antiviral drug targets against this class of human pathogens is one of the significant healthcare needs. Nucleocapsid proteins of negative strand RNA viruses wrap the viral genomic RNA and play essential roles in gene transcription and genome replication. Chandipura virus, a member of the Rhabdoviridae family, has a negative strand RNA genome. In addition to wrapping the genomic RNA, its nucleocapsid protein interacts with the positive strand leader RNA and plays a vital role in the virus life-cycle. We have designed a peptide, based on prior knowledge and demonstrated that the peptide is capable of binding specifically to the positive strand leader RNA. When the peptide was transported inside the cell, it inhibited viral growth with IC values in the low micromolar range. Given the widespread occurrence of leader RNAs in negative strand RNA viruses and its interaction with the nucleocapsid protein, it is likely that this interaction could be a valid drug target for other negative strand RNA viruses.
Topics: Genome, Viral; Humans; Nucleocapsid Proteins; RNA Viruses; RNA, Viral; Vesiculovirus; Virus Replication
PubMed: 33508356
DOI: 10.1016/j.virusres.2021.198298 -
Virology Journal May 2024The Cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) serves as a key innate immune signaling axis involved in the regulation of various human... (Review)
Review
The Cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) serves as a key innate immune signaling axis involved in the regulation of various human diseases. It has been found that cGAS-STING pathway can recognize a variety of cytosolic double-stranded DNA (dsDNA), contributing to cause a robust type I interferon response thereby affecting the occurrence and progression of viral infection. Accumulating evidence indicates RNA virus-derived components play an important role in regulating cGAS-STING signaling, either as protective or pathogenic factors in the pathogenesis of diseases. Thus, a comprehensive understanding of the function of RNA virus-derived components in regulating cGAS-STING signaling will provide insights into developing novel therapies. Here, we review the existing literature on cGAS-STING pathway regulated by RNA virus-derived components to propose insights into pharmacologic strategies targeting the cGAS-STING pathway.
Topics: Nucleotidyltransferases; Humans; Signal Transduction; Membrane Proteins; RNA Viruses; Immunity, Innate; Animals; Interferon Type I
PubMed: 38693578
DOI: 10.1186/s12985-024-02359-1 -
Viruses Oct 2019Positive-sense single-stranded RNA (+ssRNA) viruses comprise many (re-)emerging human pathogens that pose a public health problem. Our innate immune system and, in... (Review)
Review
Positive-sense single-stranded RNA (+ssRNA) viruses comprise many (re-)emerging human pathogens that pose a public health problem. Our innate immune system and, in particular, the interferon response form the important first line of defence against these viruses. Given their genetic flexibility, these viruses have therefore developed multiple strategies to evade the innate immune response in order to optimize their replication capacity. Already many molecular mechanisms of innate immune evasion by +ssRNA viruses have been identified. However, research addressing the effect of host innate immune evasion on the pathology caused by viral infections is less prevalent in the literature, though very relevant and interesting. Since interferons have been implicated in inflammatory diseases and immunopathology in addition to their protective role in infection, antagonizing the immune response may have an ambiguous effect on the clinical outcome of the viral disease. Therefore, this review discusses what is currently known about the role of interferons and host immune evasion in the pathogenesis of emerging coronaviruses, alphaviruses and flaviviruses.
Topics: Alphavirus; Animals; Clinical Trials as Topic; Coronavirus; Flavivirus; Host Microbial Interactions; Humans; Immune Evasion; Immunity, Innate; Interferons; Mice; RNA Virus Infections; RNA Viruses; Virus Replication
PubMed: 31635238
DOI: 10.3390/v11100961 -
A decade after the generation of a negative-sense RNA virus from cloned cDNA - what have we learned?The Journal of General Virology Nov 2002Since the first generation of a negative-sense RNA virus entirely from cloned cDNA in 1994, similar reverse genetics systems have been established for members of most... (Review)
Review
Since the first generation of a negative-sense RNA virus entirely from cloned cDNA in 1994, similar reverse genetics systems have been established for members of most genera of the Rhabdo- and Paramyxoviridae families, as well as for Ebola virus (Filoviridae). The generation of segmented negative-sense RNA viruses was technically more challenging and has lagged behind the recovery of nonsegmented viruses, primarily because of the difficulty of providing more than one genomic RNA segment. A member of the Bunyaviridae family (whose genome is composed of three RNA segments) was first generated from cloned cDNA in 1996, followed in 1999 by the production of influenza virus, which contains eight RNA segments. Thus, reverse genetics, or the de novo synthesis of negative-sense RNA viruses from cloned cDNA, has become a reliable laboratory method that can be used to study this large group of medically and economically important viruses. It provides a powerful tool for dissecting the virus life cycle, virus assembly, the role of viral proteins in pathogenicity and the interplay of viral proteins with components of the host cell immune response. Finally, reverse genetics has opened the way to develop live attenuated virus vaccines and vaccine vectors.
Topics: Animals; DNA, Complementary; Genetic Vectors; Glycoproteins; Humans; Orthomyxoviridae; Phosphoproteins; RNA Viruses; Transcription, Genetic; Viral Proteins; Virus Replication
PubMed: 12388800
DOI: 10.1099/0022-1317-83-11-2635 -
Plant Biotechnology Journal Aug 2018Recently, CRISPR-Cas (clustered, regularly interspaced short palindromic repeats-CRISPR-associated proteins) system has been used to produce plants resistant to DNA...
Recently, CRISPR-Cas (clustered, regularly interspaced short palindromic repeats-CRISPR-associated proteins) system has been used to produce plants resistant to DNA virus infections. However, there is no RNA virus control method in plants that uses CRISPR-Cas system to target the viral genome directly. Here, we reprogrammed the CRISPR-Cas9 system from Francisella novicida to confer molecular immunity against RNA viruses in Nicotiana benthamiana and Arabidopsis plants. Plants expressing FnCas9 and sgRNA specific for the cucumber mosaic virus (CMV) or tobacco mosaic virus (TMV) exhibited significantly attenuated virus infection symptoms and reduced viral RNA accumulation. Furthermore, in the transgenic virus-targeting plants, the resistance was inheritable and the progenies showed significantly less virus accumulation. These data reveal that the CRISPR/Cas9 system can be used to produce plant that stable resistant to RNA viruses, thereby broadening the use of such technology for virus control in agricultural field.
Topics: CRISPR-Cas Systems; Francisella; Plant Diseases; Plants, Genetically Modified; RNA Viruses
PubMed: 29327438
DOI: 10.1111/pbi.12881 -
PLoS Pathogens May 2018
Topics: Animals; Cytoplasm; Genome, Viral; Host-Pathogen Interactions; Humans; MicroRNAs; Models, Biological; RNA Processing, Post-Transcriptional; RNA Virus Infections; RNA Viruses; RNA, Viral; Virus Replication
PubMed: 29852025
DOI: 10.1371/journal.ppat.1006963 -
Advances in Virus Research 2024RNA viruses are some of the most successful biological entities due their ability to adapt and evolve. Despite their small genome and parasitic nature, RNA viruses have... (Review)
Review
RNA viruses are some of the most successful biological entities due their ability to adapt and evolve. Despite their small genome and parasitic nature, RNA viruses have evolved many mechanisms to ensure their survival and maintenance in the host population. We propose that one of these mechanisms of survival is the generation of nonstandard viral genomes (nsVGs) that accumulate during viral replication. NsVGs are often considered to be accidental defective byproducts of the RNA virus replication, but their ubiquity and the plethora of roles they have during infection indicate that they are an integral part of the virus life cycle. Here we review the different types of nsVGs and discuss how their multiple roles during infection could be beneficial for RNA viruses to be maintained in nature. By shifting our perspectives on what makes a virus successful, we posit that nsVG generation is a conserved phenomenon that arose during RNA virus evolution as an essential component of a healthy virus community.
Topics: RNA Viruses; Genome, Viral; Evolution, Molecular; Virus Replication; Humans; Animals; RNA, Viral; RNA Virus Infections
PubMed: 38897708
DOI: 10.1016/bs.aivir.2024.05.002