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Annual Review of Virology Sep 2020Seasonal influenza vaccines prevent influenza-related illnesses, hospitalizations, and deaths. However, these vaccines are not as effective as other viral vaccines, and... (Review)
Review
Seasonal influenza vaccines prevent influenza-related illnesses, hospitalizations, and deaths. However, these vaccines are not as effective as other viral vaccines, and there is clearly room for improvement. Here, we review the history of seasonal influenza vaccines, describe challenges associated with producing influenza vaccine antigens, and discuss the inherent difficulties of updating influenza vaccine strains each influenza season. We argue that seasonal influenza vaccines can be dramatically improved by modernizing antigen production processes and developing models that are better at predicting viral evolution. Resources should be specifically dedicated to improving seasonal influenza vaccines while developing entirely new vaccine platforms.
Topics: Antigenic Variation; Evolution, Molecular; History, 20th Century; Humans; Immunogenicity, Vaccine; Influenza Vaccines; Influenza, Human; Orthomyxoviridae
PubMed: 32392457
DOI: 10.1146/annurev-virology-010320-044746 -
Blood Dec 2022
Topics: Humans; Antigenic Drift and Shift; Leukemia; Lymphoma; Killer Cells, Natural; Induced Pluripotent Stem Cells
PubMed: 36480219
DOI: 10.1182/blood.2022017794 -
Microbiology Spectrum Feb 2015The genus Neisseria contains two pathogenic species of prominant public health concern: Neisseria gonorrhoeae and Neisseria meningitidis. These pathogens display a... (Review)
Review
The genus Neisseria contains two pathogenic species of prominant public health concern: Neisseria gonorrhoeae and Neisseria meningitidis. These pathogens display a notable ability to undergo frequent programmed recombination events. The recombination-mediated pathways of transformation and pilin antigenic variation in the Neisseria are well-studied systems that are critical for pathogenesis. Here we will detail the conserved and unique aspects of transformation and antigenic variation in the Neisseria. Transformation will be followed from initial DNA binding through recombination into the genome with consideration to the factors necessary at each step. Additional focus is paid to the unique type IV secretion system that mediates donation of transforming DNA in the pathogenic Neisseria. The pilin antigenic variation system uses programmed recombinations to alter a major surface determinant, which allows immune avoidance and promotes infection. We discuss the trans- and cis- acting factors which facilitate pilin antigenic variation and present the current understanding of the mechanisms involved in the process.
Topics: Antigenic Variation; Antigens, Bacterial; Biological Transport; DNA Transformation Competence; DNA, Bacterial; Fimbriae Proteins; Humans; Immune Evasion; Interspersed Repetitive Sequences; Neisseria gonorrhoeae; Neisseria meningitidis; Recombination, Genetic; Type IV Secretion Systems
PubMed: 26104562
DOI: 10.1128/microbiolspec.MDNA3-0015-2014 -
Trends in Microbiology Feb 2019G-quadruplexes (G4s) are noncanonical nucleic acid secondary structures formed by guanine-rich DNA and RNA sequences. In this review we aim to provide an overview of the... (Review)
Review
G-quadruplexes (G4s) are noncanonical nucleic acid secondary structures formed by guanine-rich DNA and RNA sequences. In this review we aim to provide an overview of the biological roles of G4s in microbial genomes with emphasis on recent discoveries. G4s are enriched and conserved in the regulatory regions of microbes, including bacteria, fungi, and viruses. Importantly, G4s in hepatitis B virus (HBV) and hepatitis C virus (HCV) genomes modulate genes crucial for virus replication. Recent studies on Epstein-Barr virus (EBV) shed light on the role of G4s within the microbial transcripts as cis-acting regulatory signals that modulate translation and facilitate immune evasion. Furthermore, G4s in microbial genomes have been linked to radioresistance, antigenic variation, recombination, and latency. G4s in microbial genomes represent novel therapeutic targets for antimicrobial therapy.
Topics: Antigenic Variation; Bacteria; Base Sequence; Carrier Proteins; Fungi; G-Quadruplexes; Gene Expression Regulation; Genome, Microbial; Herpesvirus 4, Human; Humans; RNA Editing; Radiation Tolerance; Recombination, Genetic; Virion; Virulence; Virus Assembly; Virus Latency; Virus Replication; Viruses
PubMed: 30224157
DOI: 10.1016/j.tim.2018.08.011 -
Trends in Parasitology Jan 2022An intriguing and remarkable feature of African trypanosomes is their antigenic variation system, mediated by the variant surface glycoprotein (VSG) family and... (Review)
Review
An intriguing and remarkable feature of African trypanosomes is their antigenic variation system, mediated by the variant surface glycoprotein (VSG) family and fundamental to both immune evasion and disease epidemiology within host populations. Recent studies have revealed that the VSG repertoire has a complex evolutionary history. Sequence diversity, genomic organization, and expression patterns are species-specific, which may explain other variations in parasite virulence and disease pathology. Evidence also shows that we may be underestimating the extent to what VSGs are repurposed beyond their roles as variant antigens, establishing a need to examine VSG functionality more deeply. Here, we review sequence variation within the VSG gene family, and highlight the many opportunities to explore their likely diverse contributions to parasite survival.
Topics: Animals; Antigenic Variation; Membrane Glycoproteins; Trypanosoma; Trypanosoma brucei brucei; Trypanosomiasis, African; Variant Surface Glycoproteins, Trypanosoma
PubMed: 34376326
DOI: 10.1016/j.pt.2021.07.012 -
Current Opinion in Microbiology Dec 2022Survival of the African trypanosome within its mammalian hosts, and hence transmission between hosts, relies upon antigenic variation, where stochastic changes in the... (Review)
Review
Survival of the African trypanosome within its mammalian hosts, and hence transmission between hosts, relies upon antigenic variation, where stochastic changes in the composition of their protective variant-surface glycoprotein (VSG) coat thwart effective removal of the pathogen by adaptive immunity. Antigenic variation has evolved remarkable mechanistic complexity in Trypanosoma brucei, with switching of the VSG coat executed by either transcriptional or recombination reactions. In the former, a single T. brucei cell selectively transcribes one telomeric VSG transcription site, termed the expression site (ES), from a pool of around 15. Silencing of the active ES and activation of one previously silent ES can lead to a co-ordinated VSG coat switch. Outside the ESs, the T. brucei genome contains an enormous archive of silent VSG genes and pseudogenes, which can be recombined into the ES to execute a coat switch. Most such recombination involves gene conversion, including copying of a complete VSG and more complex reactions where novel 'mosaic' VSGs are formed as patchworks of sequences from several silent (pseudo)genes. Understanding of the cellular machinery that directs transcriptional and recombination VSG switching is growing rapidly and the emerging picture is of the use of proteins, complexes and pathways that are not limited to trypanosomes, but are shared across the wider grouping of kinetoplastids and beyond, suggesting co-option of widely used, core cellular reactions. We will review what is known about the machinery of antigenic variation and discuss if there remains the possibility of trypanosome adaptations, or even trypanosome-specific machineries, that might offer opportunities to impair this crucial parasite-survival process.
Topics: Animals; Variant Surface Glycoproteins, Trypanosoma; Antigenic Variation; Trypanosoma; Trypanosoma brucei brucei; Genome; Mammals
PubMed: 36215868
DOI: 10.1016/j.mib.2022.102209 -
Journal of Immunology (Baltimore, Md. :... Jan 2019The diversity of Ag-specific adaptive receptors on the surface of B cells and in the population of secreted Abs is enormous, but increasingly, we are acquiring the... (Review)
Review
The diversity of Ag-specific adaptive receptors on the surface of B cells and in the population of secreted Abs is enormous, but increasingly, we are acquiring the technical capability to interrogate Ab repertoires in great detail. These Ab technologies have been especially pointed at understanding the complex issues of immunity to infection and disease caused by influenza virus, one of the most common and vexing medical problems in man. Influenza immunity is particularly interesting as a model system because the antigenic diversity of influenza strains and proteins is high and constantly evolving. Discovery of canonical features in the subset of the influenza repertoire response that is broadly reactive for diverse influenza strains has spurred the recent optimism for creating universal influenza vaccines. Using new technologies for sequencing Ab repertoires at great depth is helping us to understand the central features of influenza immunity.
Topics: Antibodies, Viral; Antibody Diversity; Antigenic Variation; Antigens, Viral; B-Lymphocytes; Humans; Influenza A virus; Influenza Vaccines; Influenza, Human; Receptors, Antigen, B-Cell
PubMed: 30617118
DOI: 10.4049/jimmunol.1801459 -
Proceedings of the National Academy of... Oct 2023Antigenic variation is the main immune escape mechanism for RNA viruses like influenza or SARS-CoV-2. While high mutation rates promote antigenic escape, they also...
Antigenic variation is the main immune escape mechanism for RNA viruses like influenza or SARS-CoV-2. While high mutation rates promote antigenic escape, they also induce large mutational loads and reduced fitness. It remains unclear how this cost-benefit trade-off selects the mutation rate of viruses. Using a traveling wave model for the coevolution of viruses and host immune systems in a finite population, we investigate how immunity affects the evolution of the mutation rate and other nonantigenic traits, such as virulence. We first show that the nature of the wave depends on how cross-reactive immune systems are, reconciling previous approaches. The immune-virus system behaves like a Fisher wave at low cross-reactivities, and like a fitness wave at high cross-reactivities. These regimes predict different outcomes for the evolution of nonantigenic traits. At low cross-reactivities, the evolutionarily stable strategy is to maximize the speed of the wave, implying a higher mutation rate and increased virulence. At large cross-reactivities, where our estimates place H3N2 influenza, the stable strategy is to increase the basic reproductive number, keeping the mutation rate to a minimum and virulence low.
Topics: Humans; Influenza, Human; Influenza A Virus, H3N2 Subtype; Antigenic Variation; RNA Viruses; Hemagglutinin Glycoproteins, Influenza Virus
PubMed: 37871216
DOI: 10.1073/pnas.2307712120 -
Viruses Apr 2016Antigenic drift and genetic variation are significantly constrained in measles virus (MeV). Genetic stability of MeV is exceptionally high, both in the lab and in the... (Review)
Review
Antigenic drift and genetic variation are significantly constrained in measles virus (MeV). Genetic stability of MeV is exceptionally high, both in the lab and in the field, and few regions of the genome allow for rapid genetic change. The regions of the genome that are more tolerant of mutations (i.e., the untranslated regions and certain domains within the N, C, V, P, and M proteins) indicate genetic plasticity or structural flexibility in the encoded proteins. Our analysis reveals that strong constraints in the envelope proteins (F and H) allow for a single serotype despite known antigenic differences among its 24 genotypes. This review describes some of the many variables that limit the evolutionary rate of MeV. The high genomic stability of MeV appears to be a shared property of the Paramyxovirinae, suggesting a common mechanism that biologically restricts the rate of mutation.
Topics: Adaptation, Biological; Animals; Antigenic Variation; Genetic Variation; Genomic Instability; Genotype; Humans; Measles; Measles virus; Mutation; Open Reading Frames; Serogroup; Untranslated Regions; Viral Proteins
PubMed: 27110809
DOI: 10.3390/v8040109 -
Frontiers in Immunology 2020Relapsing fever (RF) is claimed a neglected arthropod-borne disease caused by a number of diverse human pathogenic (.) species. These RF borreliae are separated into... (Review)
Review
Relapsing fever (RF) is claimed a neglected arthropod-borne disease caused by a number of diverse human pathogenic (.) species. These RF borreliae are separated into the groups of tick-transmitted species including , and , and the louse-borne species . As typical blood-borne pathogens achieving high cell concentrations in human blood, RF borreliae (RFB) must outwit innate immunity, in particular complement as the first line of defense. One prominent strategy developed by RFB to evade innate immunity involves inactivation of complement by recruiting distinct complement regulatory proteins, e.g., C1 esterase inhibitor (C1-INH), C4b-binding protein (C4BP), factor H (FH), FH-like protein-1 (FHL-1), and factor H-related proteins FHR-1 and FHR-2, or binding of individual complement components and plasminogen, respectively. A number of multi-functional, complement and plasminogen-binding molecules from distinct species have previously been identified and characterized, exhibiting considerable heterogeneity in their sequences, structures, gene localization, and their capacity to bind host-derived proteins. In addition, RFB possess a unique system of antigenic variation, allowing them to change the composition of surface-exposed variable major proteins, thus evading the acquired immune response of the human host. This review focuses on the current knowledge of the immune evasion strategies by RFB and highlights the role of complement-interfering and infection-associated molecules for the pathogenesis of RFB.
Topics: Adaptive Immunity; Antigenic Variation; Bacterial Proteins; Borrelia; Complement System Proteins; Humans; Immune Evasion; Immunity, Innate; Protein Binding; Relapsing Fever
PubMed: 32793216
DOI: 10.3389/fimmu.2020.01560