-
Viruses Aug 2019RNA viruses represent a large and important group of pathogens that infect a broad range of hosts. Segmented RNA viruses are a subclass of this group that encode their... (Review)
Review
RNA viruses represent a large and important group of pathogens that infect a broad range of hosts. Segmented RNA viruses are a subclass of this group that encode their genomes in two or more molecules and package all of their RNA segments in a single virus particle. These divided genomes come in different forms, including double-stranded RNA, coding-sense single-stranded RNA, and noncoding single-stranded RNA. Genera that possess these genome types include, respectively, (e.g., Bluetongue virus), (e.g., Red clover necrotic mosaic virus) and (e.g., Influenza A virus). Despite their distinct genomic features and diverse host ranges (i.e., animals, plants, and humans, respectively) each of these viruses uses -acting RNA-RNA interactions (tRRIs) to facilitate co-packaging of their segmented genome. The tRRIs occur between different viral genome segments and direct the selective packaging of a complete genome complement. Here we explore the current state of understanding of tRRI-mediated co-packaging in the abovementioned viruses and examine other known and potential functions for this class of RNA-RNA interaction.
Topics: Animals; Gene Expression Regulation, Viral; Humans; RNA Viruses; RNA, Viral; Transcriptional Activation; Virus Assembly; Virus Diseases
PubMed: 31416187
DOI: 10.3390/v11080751 -
Microbiology and Molecular Biology... Sep 2022Negative-sense RNA virus populations are composed of diverse viral components that interact to form a community and shape the outcome of virus infections. At the genomic... (Review)
Review
Negative-sense RNA virus populations are composed of diverse viral components that interact to form a community and shape the outcome of virus infections. At the genomic level, RNA virus populations consist not only of a homogeneous population of standard viral genomes but also of an extremely large number of genome variants, termed viral quasispecies, and nonstandard viral genomes, which include copy-back viral genomes, deletion viral genomes, mini viral RNAs, and hypermutated RNAs. At the particle level, RNA virus populations are composed of pleomorphic particles, particles missing or having additional genomes, and single particles or particle aggregates. As we continue discovering more about the components of negative-sense RNA virus populations and their crucial functions during virus infection, it will become more important to study RNA virus populations as a whole rather than their individual parts. In this review, we will discuss what is known about the components of negative-sense RNA virus communities, speculate how the components of the virus community interact, and summarize what vaccines and antiviral therapies are being currently developed to target or harness these components.
Topics: Antiviral Agents; Genome, Viral; Negative-Sense RNA Viruses; RNA Viruses; RNA, Viral; Virus Assembly
PubMed: 35658541
DOI: 10.1128/mmbr.00086-21 -
International Journal of Molecular... Sep 2019RNA viruses are known to replicate by low fidelity polymerases and have high mutation rates whereby the resulting virus population tends to exist as a distribution of... (Review)
Review
RNA viruses are known to replicate by low fidelity polymerases and have high mutation rates whereby the resulting virus population tends to exist as a distribution of mutants. In this review, we aim to explore how genetic events such as spontaneous mutations could alter the genomic organization of RNA viruses in such a way that they impact virus replications and plaque morphology. The phenomenon of quasispecies within a viral population is also discussed to reflect virulence and its implications for RNA viruses. An understanding of how such events occur will provide further evidence about whether there are molecular determinants for plaque morphology of RNA viruses or whether different plaque phenotypes arise due to the presence of quasispecies within a population. Ultimately this review gives an insight into whether the intrinsically high error rates due to the low fidelity of RNA polymerases is responsible for the variation in plaque morphology and diversity in virulence. This can be a useful tool in characterizing mechanisms that facilitate virus adaptation and evolution.
Topics: Animals; DNA-Directed RNA Polymerases; Evolution, Molecular; Humans; Quasispecies; RNA Viruses; Viral Proteins; Virulence
PubMed: 31546962
DOI: 10.3390/ijms20184657 -
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 -
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 -
Frontiers in Immunology 2020Complement, a part of the innate arm of the immune system, is integral to the frontline defense of the host against innumerable pathogens, which includes RNA viruses.... (Review)
Review
Complement, a part of the innate arm of the immune system, is integral to the frontline defense of the host against innumerable pathogens, which includes RNA viruses. Among the major groups of viruses, RNA viruses contribute significantly to the global mortality and morbidity index associated with viral infection. Despite multiple routes of entry adopted by these viruses, facing complement is inevitable. The initial interaction with complement and the nature of this interaction play an important role in determining host resistance versus susceptibility to the viral infection. Many RNA viruses are potent activators of complement, often resulting in virus neutralization. Yet, another facet of virus-induced activation is the exacerbation in pathogenesis contributing to the overall morbidity. The severity in disease and death associated with RNA virus infections shows a tip in the scale favoring viruses. Growing evidence suggest that like their DNA counterparts, RNA viruses have co-evolved to master ingenious strategies to remarkably restrict complement. Modulation of host genes involved in antiviral responses contributed prominently to the adoption of unique strategies to keep complement at bay, which included either down regulation of activation components (C3, C4) or up regulation of complement regulatory proteins. All this hints at a possible "hijacking" of the cross-talk mechanism of the host immune system. Enveloped RNA viruses have a selective advantage of not only modulating the host responses but also recruiting membrane-associated regulators of complement activation (RCAs). This review aims to highlight the significant progress in the understanding of RNA virus-complement interactions.
Topics: Adaptive Immunity; Animals; Complement Activation; Complement System Proteins; Evolution, Molecular; Gene Expression Regulation, Viral; Host-Pathogen Interactions; Humans; Immunity, Innate; RNA Virus Infections; RNA Viruses; Severity of Illness Index
PubMed: 33133089
DOI: 10.3389/fimmu.2020.573583 -
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 -
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 -
Viruses Jun 2014RNA viruses are capable of rapid spread and severe or potentially lethal disease in both animals and humans. The development of reverse genetics systems for... (Review)
Review
RNA viruses are capable of rapid spread and severe or potentially lethal disease in both animals and humans. The development of reverse genetics systems for manipulation and study of RNA virus genomes has provided platforms for designing and optimizing viral mutants for vaccine development. Here, we review the impact of RNA virus reverse genetics systems on past and current efforts to design effective and safe viral therapeutics and vaccines.
Topics: Animals; Coronaviridae; Flaviviridae; Genetic Engineering; Genome, Viral; Humans; Orthomyxoviridae; Paramyxoviridae; RNA Virus Infections; Reverse Genetics; Viral Vaccines
PubMed: 24967693
DOI: 10.3390/v6072531 -
The Journal of General Virology Mar 2021A long-standing paradigm in virology was that non-enveloped viruses induce cell lysis to release progeny virions. However, emerging evidence indicates that some... (Review)
Review
A long-standing paradigm in virology was that non-enveloped viruses induce cell lysis to release progeny virions. However, emerging evidence indicates that some non-enveloped viruses exit cells without inducing cell lysis, while others engage both lytic and non-lytic egress mechanisms. Enteric viruses are transmitted via the faecal-oral route and are important causes of a wide range of human infections, both gastrointestinal and extra-intestinal. Virus cellular egress, when fully understood, may be a relevant target for antiviral therapies, which could minimize the public health impact of these infections. In this review, we outline lytic and non-lytic cell egress mechanisms of non-enveloped enteric RNA viruses belonging to five families: , , , and . We discuss factors that contribute to egress mechanisms and the relevance of these mechanisms to virion stability, infectivity and transmission. Since most data were obtained in traditional two-dimensional cell cultures, we will further attempt to place them into the context of polarized cultures and pathogenesis. Throughout the review, we highlight numerous knowledge gaps to stimulate future research into the egress mechanisms of these highly prevalent but largely understudied viruses.
Topics: Animals; Humans; RNA Virus Infections; RNA Viruses; Virion; Virus Release
PubMed: 33560198
DOI: 10.1099/jgv.0.001557