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Clinical Microbiology Reviews Jul 2004Phase and antigenic variation result in a heterogenic phenotype of a clonal bacterial population, in which individual cells either express the phase-variable protein(s)... (Review)
Review
Phase and antigenic variation result in a heterogenic phenotype of a clonal bacterial population, in which individual cells either express the phase-variable protein(s) or not, or express one of multiple antigenic forms of the protein, respectively. This form of regulation has been identified mainly, but by no means exclusively, for a wide variety of surface structures in animal pathogens and is implicated as a virulence strategy. This review provides an overview of the many bacterial proteins and structures that are under the control of phase or antigenic variation. The context is mainly within the role of the proteins and variation for pathogenesis, which reflects the main body of literature. The occurrence of phase variation in expression of genes not readily recognizable as virulence factors is highlighted as well, to illustrate that our current knowledge is incomplete. From recent genome sequence analysis, it has become clear that phase variation may be more widespread than is currently recognized, and a brief discussion is included to show how genome sequence analysis can provide novel information, as well as its limitations. The current state of knowledge of the molecular mechanisms leading to phase variation and antigenic variation are reviewed, and the way in which these mechanisms form part of the general regulatory network of the cell is addressed. Arguments both for and against a role of phase and antigenic variation in immune evasion are presented and put into new perspective by distinguishing between a role in bacterial persistence in a host and a role in facilitating evasion of cross-immunity. Finally, examples are presented to illustrate that phase-variable gene expression should be taken into account in the development of diagnostic assays and in the interpretation of experimental results and epidemiological studies.
Topics: Amino Acid Sequence; Antigenic Variation; Bacteria; Bacterial Proteins; Base Sequence; Gene Expression Regulation, Bacterial; Humans; Molecular Sequence Data
PubMed: 15258095
DOI: 10.1128/CMR.17.3.581-611.2004 -
Cellular Microbiology Dec 2013African trypanosomes are lethal human and animal parasites that use antigenic variation for evasion of host adaptive immunity. To facilitate antigenic variation,... (Review)
Review
African trypanosomes are lethal human and animal parasites that use antigenic variation for evasion of host adaptive immunity. To facilitate antigenic variation, trypanosomes dedicate approximately one third of their nuclear genome, including many minichromosomes, and possibly all sub-telomeres, to variant surface glycoprotein (VSG) genes and associated sequences. Antigenic variation requires transcription of a single VSG by RNA polymerase I (Pol-I), with silencing of other VSGs, and periodic switching of the expressed gene, typically via DNA recombination with duplicative translocation of a new VSG to the active site. Thus, telomeric location, epigenetic controls and monoallelic transcription by Pol-I at an extranucleolar site are prominent features of VSGs and their expression, with telomeres, chromatin structure and nuclear organization all making vitally important contributions to monoallelic VSG expression control and switching. We discuss VSG transcription, recombination and replication control within this chromosomal and sub-nuclear context.
Topics: Antigenic Variation; Chromatin; DNA Breaks, Double-Stranded; DNA Repair; Humans; RNA Polymerase I; Recombination, Genetic; Telomere; Transcription, Genetic; Trypanosoma brucei gambiense; Trypanosomiasis, African; Variant Surface Glycoproteins, Trypanosoma
PubMed: 24047558
DOI: 10.1111/cmi.12215 -
Research in Microbiology 1992Antigenic variation and strain heterogeneity have been demonstrated for the pathogenic Borrelia species, i.e. B. burgdorferi and the relapsing fever borreliae. In... (Review)
Review
Antigenic variation and strain heterogeneity have been demonstrated for the pathogenic Borrelia species, i.e. B. burgdorferi and the relapsing fever borreliae. In relapsing fever, new borrelia serotypes emerge at a high rate spontaneously, a mechanism that is caused by DNA rearrangements on linear plasmid translocating genes coding for variable major proteins from previous silent to expression sites (i.e. from inner sites to telomeric sites of the plasmid). As a result of this variation, the borreliae escape the immune response of the host, thus leading to the relapse phenomenon. In B. burgdorferi, which is the causative agent of the multisystem disorder Lyme borreliosis, there is also a growing body of findings that antigenic variation is involved in pathogenesis of the disease. Phenotypic variation of strains in vitro concerns the size and the amount of surface-associated proteins (OspA, OspB and pC). There are indications that OspA and OspB truncations are due to deletions within the ospAB operon caused by recombination events, and that OspA/OspB-less mutants lack the 49-kb plasmid that bears the ospAB operon. With the increasing number of isolates obtained from various geographic and biological sources, it became apparent that B. burgdorferi is immunologically and genetically more heterogeneous, as previously believed. The major outer surface proteins OspA and OspB (which have been efficient antigens in vaccine studies) are heterogeneous at a genetic level. The same degree of genetic non-identity was observed for the pC protein. Other proteins like flagellin and the highly specific immunodominant p100 range protein show a lower degree of non-identity. Recombinant OspA, pC, p100 range protein and flagellin have been hyperexpressed in E. coli and these proteins are immunologically reactive. This allows further research for development of vaccines and diagnostic tools. B. burgdorferi isolates have been investigated with genotyping (DNA hybridization, PCR and 16S rRNA analysis) as well as serotyping by various authors. Comparison of the different methods has shown good agreement when the same strains have been investigated. No correlation could be found between different phenotypic and genotypic groups with respect to the ability to cause arthritis in SCID mice. A serotyping system based on immunological differences in OspA detected by a panel of monoclonal antibodies has been proposed. Serotyping a large number of B. burgdorferi isolates has shown a striking predominance of the OspA serotype 2 among European isolates from human skin, in contrast to isolates from ticks or CSF.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Antigenic Variation; Bacterial Outer Membrane Proteins; Borrelia burgdorferi Group; Flagellin; In Vitro Techniques; Recombination, Genetic; Serotyping
PubMed: 1475519
DOI: 10.1016/0923-2508(92)90116-6 -
Journal of Virology Jun 2020Low-pathogenic avian influenza viruses (LPAIVs) are genetically highly variable and have diversified into multiple evolutionary lineages that are primarily associated...
Low-pathogenic avian influenza viruses (LPAIVs) are genetically highly variable and have diversified into multiple evolutionary lineages that are primarily associated with wild-bird reservoirs. Antigenic variation has been described for mammalian influenza viruses and for highly pathogenic avian influenza viruses that circulate in poultry, but much less is known about antigenic variation of LPAIVs. In this study, we focused on H13 and H16 LPAIVs that circulate globally in gulls. We investigated the evolutionary history and intercontinental gene flow based on the hemagglutinin (HA) gene and used representative viruses from genetically distinct lineages to determine their antigenic properties by hemagglutination inhibition assays. For H13, at least three distinct genetic clades were evident, while for H16, at least two distinct genetic clades were evident. Twenty and ten events of intercontinental gene flow were identified for H13 and H16 viruses, respectively. At least two antigenic variants of H13 and at least one antigenic variant of H16 were identified. Amino acid positions in the HA protein that may be involved in the antigenic variation were inferred, and some of the positions were located near the receptor binding site of the HA protein, as they are in the HA protein of mammalian influenza A viruses. These findings suggest independent circulation of H13 and H16 subtypes in gull populations, as antigenic patterns do not overlap, and they contribute to the understanding of the genetic and antigenic variation of LPAIVs naturally circulating in wild birds. Wild birds play a major role in the epidemiology of low-pathogenic avian influenza viruses (LPAIVs), which are occasionally transmitted-directly or indirectly-from them to other species, including domestic animals, wild mammals, and humans, where they can cause subclinical to fatal disease. Despite a multitude of genetic studies, the antigenic variation of LPAIVs in wild birds is poorly understood. Here, we investigated the evolutionary history, intercontinental gene flow, and antigenic variation among H13 and H16 LPAIVs. The circulation of subtypes H13 and H16 seems to be maintained by a narrower host range, in particular gulls, than the majority of LPAIV subtypes and may therefore serve as a model for evolution and epidemiology of H1 to H12 LPAIVs in wild birds. The findings suggest that H13 and H16 LPAIVs circulate independently of each other and emphasize the need to investigate within-clade antigenic variation of LPAIVs in wild birds.
Topics: Animals; Animals, Wild; Antigenic Variation; Birds; Charadriiformes; Hemagglutination Inhibition Tests; Hemagglutinin Glycoproteins, Influenza Virus; Hemagglutinins; Host Specificity; Influenza A virus; Influenza in Birds; Phylogeny; Phylogeography
PubMed: 32321814
DOI: 10.1128/JVI.00537-20 -
BioEssays : News and Reviews in... Dec 2018The process of antigenic variation in parasitic African trypanosomes is a remarkable mechanism for outwitting the immune system of the mammalian host, but it requires a... (Review)
Review
The process of antigenic variation in parasitic African trypanosomes is a remarkable mechanism for outwitting the immune system of the mammalian host, but it requires a delicate balancing act for the monoallelic expression, folding and transport of a single variant surface glycoprotein (VSG). Only one of hundreds of VSG genes is expressed at time, and this from just one of ≈15 dedicated expression sites. By switching expression of VSGs the parasite presents a continuously shifting antigenic facade leading to prolonged chronic infections lasting months to years. The basics of VSG structure and switching have been known for several decades, but recent studies have brought higher resolution to many aspects this process. New VSG structures, in silico modeling of infections, studies of VSG codon usage, and experimental ablation of VSG expression provide insights that inform how this remarkable system may have evolved.
Topics: Africa; Antigenic Variation; Gene Expression Regulation; Membrane Glycoproteins; Protozoan Proteins; Trypanosoma
PubMed: 30370931
DOI: 10.1002/bies.201800181 -
Emerging Infectious Diseases 2000Several pathogens of humans and domestic animals depend on hematophagous arthropods to transmit them from one vertebrate reservoir host to another and maintain them in... (Review)
Review
Several pathogens of humans and domestic animals depend on hematophagous arthropods to transmit them from one vertebrate reservoir host to another and maintain them in an environment. These pathogens use antigenic variation to prolong their circulation in the blood and thus increase the likelihood of transmission. By convergent evolution, bacterial and protozoal vector-borne pathogens have acquired similar genetic mechanisms for successful antigenic variation. Borrelia spp. and Anaplasma marginale (among bacteria) and African trypanosomes, Plasmodium falciparum, and Babesia bovis (among parasites) are examples of pathogens using these mechanisms. Antigenic variation poses a challenge in the development of vaccines against vector-borne pathogens.
Topics: Anaplasma; Animals; Antigenic Variation; Babesia bovis; Bacterial Infections; Borrelia; Disease Vectors; Humans; Parasitic Diseases; Plasmodium falciparum
PubMed: 10998374
DOI: 10.3201/eid0605.000502 -
Phase and antigenic variation govern competition dynamics through positioning in bacterial colonies.Scientific Reports Sep 2017Cellular positioning towards the surface of bacterial colonies and biofilms can enhance dispersal, provide a selective advantage due to increased nutrient and space...
Cellular positioning towards the surface of bacterial colonies and biofilms can enhance dispersal, provide a selective advantage due to increased nutrient and space availability, or shield interior cells from external stresses. Little is known about the molecular mechanisms that govern bacterial positioning. Using the type IV pilus (T4P) of Neisseria gonorrhoeae, we tested the hypothesis that the processes of phase and antigenic variation govern positioning and thus enhance bacterial fitness in expanding gonococcal colonies. By independently tuning growth rate and T4P-mediated interaction forces, we show that the loss of T4P and the subsequent segregation to the front confers a strong selective advantage. Sequencing of the major pilin gene of the spatially segregated sub-populations and an investigation of the spatio-temporal population dynamics was carried out. Our findings indicate that pilin phase and antigenic variation generate a standing variation of pilin sequences within the inoculation zone, while variants associated with a non-piliated phenotype segregate to the front of the growing colony. We conclude that tuning of attractive forces by phase and antigenic variation is a powerful mechanism for governing the dynamics of bacterial colonies.
Topics: Antigenic Variation; Biofilms; Fimbriae Proteins; Gonorrhea; Humans; Mutation; Neisseria gonorrhoeae
PubMed: 28939833
DOI: 10.1038/s41598-017-12472-7 -
Nature Ecology & Evolution Jan 2022Despite the propensity for complex and non-equilibrium dynamics in nature, eco-evolutionary analytical theory typically assumes that populations are at equilibria. In...
Despite the propensity for complex and non-equilibrium dynamics in nature, eco-evolutionary analytical theory typically assumes that populations are at equilibria. In particular, pathogens often show antigenic escape from host immune defences, leading to repeated epidemics, fluctuating selection and diversification, but we do not understand how this impacts the evolution of virulence. We model the impact of antigenic drift and escape on the evolution of virulence in a generalized pathogen and apply a recently introduced oligomorphic methodology that captures the dynamics of the mean and variance of traits, to show analytically that these non-equilibrium dynamics select for the long-term persistence of more acute pathogens with higher virulence. Our analysis predicts both the timings and outcomes of antigenic shifts leading to repeated epidemics and predicts the increase in variation in both antigenicity and virulence before antigenic escape. There is considerable variation in the degree of antigenic escape that occurs across pathogens and our results may help to explain the difference in virulence between related pathogens including, potentially, human influenzas. Furthermore, it follows that these pathogens will have a lower R, with clear implications for epidemic behaviour, endemic behaviour and control. More generally, our results show the importance of examining the evolutionary consequences of non-equilibrium dynamics.
Topics: Antigenic Drift and Shift; Biological Evolution; Epidemics; Humans; Phenotype; Virulence
PubMed: 34949816
DOI: 10.1038/s41559-021-01603-z -
Cellular Microbiology Dec 2013Shifts in microbial strain structure underlie both emergence of new pathogens and shifts in patterns of infection and disease of known agents. Understanding the... (Review)
Review
Shifts in microbial strain structure underlie both emergence of new pathogens and shifts in patterns of infection and disease of known agents. Understanding the selective pressures at a population level as well as the mechanisms at the molecular level represent significant gaps in our knowledge regarding microbial epidemiology. Highly antigenically variant pathogens, which are broadly represented among microbial taxa, are most commonly viewed through the mechanistic lens of how they evade immune clearance within the host. However, equally important are mechanisms that allow pathogens to evade immunity at the population level. The selective pressure of immunity at both the level of the individual host and the population is a driver of diversification within a pathogen strain. Using Anaplasma marginale as a model highly antigenically variable bacterial pathogen, we review how immunity selects for genetic diversification in alleles encoding outer membrane proteins both within and among strains. Importantly, genomic comparisons among strains isolated from diverse epidemiological settings elucidates the counterbalancing pressures for diversification and conservation, driven by immune escape and transmission fitness, respectively, and how these shape pathogen strain structure.
Topics: Anaplasma marginale; Anaplasmosis; Animals; Antigenic Variation; Antigens, Bacterial; Bacteremia; Bacterial Outer Membrane Proteins; Genetic Variation; Immune Evasion; Selection, Genetic
PubMed: 23941262
DOI: 10.1111/cmi.12182 -
Vaccine Jul 2008The relationship between influenza antigenic drift and vaccination lies at the intersection of evolutionary biology and public health, and it must be viewed and analyzed... (Review)
Review
The relationship between influenza antigenic drift and vaccination lies at the intersection of evolutionary biology and public health, and it must be viewed and analyzed in both contexts simultaneously. In this paper, 1 review what is known about the effects of antigenic drift on vaccination and the effects of vaccination on antigenic drift, and I suggest some simple ways to detect the presence of antigenic drift in seasonal influenza data. If antigenic drift occurs on the time scale of a single influenza season, it may be associated with the presence of herd immunity at the beginning of the season and may indicate a need to monitor for vaccine updates at the end of the season. The relationship between antigenic drift and vaccination must also be viewed in the context of the global circulation of influenza strains and the seeding of local and regional epidemics. In the data sets I consider--from New Zealand, New York, and France--antigenic drift can be statistically detected during some seasons, and seeding of epidemics appears to be endogenous sometimes and exogenous at other times. Improved detection of short-term antigenic drift and epidemic seeding would significantly benefit influenza monitoring efforts and vaccine selection.
Topics: Antigenic Variation; Biological Evolution; Genetic Drift; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza Vaccines; Influenza, Human; Vaccination; Virulence
PubMed: 18773534
DOI: 10.1016/j.vaccine.2008.04.011