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Nature Microbiology Aug 2023Antigenic variation as a strategy to evade the host adaptive immune response has evolved in divergent pathogens. Antigenic variation involves restricted, and often... (Review)
Review
Antigenic variation as a strategy to evade the host adaptive immune response has evolved in divergent pathogens. Antigenic variation involves restricted, and often mutually exclusive, expression of dominant antigens and a periodic switch in antigen expression during infection. In eukaryotes, nuclear compartmentalization, including three-dimensional folding of the genome and physical separation of proteins in compartments or condensates, regulates mutually exclusive gene expression and chromosomal translocations. In this Review, we discuss the impact of nuclear organization on antigenic variation in the protozoan pathogens Trypanosoma brucei and Plasmodium falciparum. In particular, we highlight the relevance of nuclear organization in both mutually exclusive antigen expression and genome stability, which underlie antigenic variation.
Topics: Animals; Parasites; Antigenic Variation; Genome; Plasmodium falciparum; Cell Nucleus; Antigens
PubMed: 37524976
DOI: 10.1038/s41564-023-01424-9 -
Current Opinion in Microbiology Aug 2016Giardia lamblia trophozoites undergo antigenic variation, where one member of the Variant-specific Surface Protein (VSP) family is expressed on the surface of... (Review)
Review
Giardia lamblia trophozoites undergo antigenic variation, where one member of the Variant-specific Surface Protein (VSP) family is expressed on the surface of proliferating trophozoites and periodically replaced by another one. Two main questions have challenged researchers since antigenic switching was discovered in Giardia: What are the mechanisms involved? How are they influenced by other cellular processes or by the environment? Two molecular mechanisms have been proposed, both involving small non-coding RNAs. Here we postulate that (a) chromatin remodeling, triggered by environmental factors, also plays an important role in selecting the VSP that will be expressed and (b) the particular VSP structure may not only protect the parasite in the small intestine but also signal the need to exchange the existing VSP for another.
Topics: Animals; Antigenic Variation; Antigens, Protozoan; Chromatin Assembly and Disassembly; Giardia lamblia; Giardiasis; Humans; MicroRNAs; Protein Conformation; Protozoan Proteins; RNA Interference; RNA, Small Interfering
PubMed: 27177351
DOI: 10.1016/j.mib.2016.04.017 -
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 -
Microbes and Infection May 2001Many intraerythrocytic hemoparasites survive the host immune system through rapid antigenic variation. Among babesial parasites antigenic variation has been demonstrated... (Review)
Review
Many intraerythrocytic hemoparasites survive the host immune system through rapid antigenic variation. Among babesial parasites antigenic variation has been demonstrated convincingly only for Babesia bovis and Babesia rodhaini. The molecular basis for antigenic variation in babesial parasites and its possible connection with cytoadherence and sequestration are discussed.
Topics: Amino Acid Sequence; Animals; Antigenic Variation; Antigens, Protozoan; Antigens, Surface; Babesia bovis; Babesiosis; Erythrocytes; Molecular Sequence Data; Plasmodium falciparum
PubMed: 11377210
DOI: 10.1016/s1286-4579(01)01404-6 -
Trends in Parasitology Apr 2019Trypanosoma brucei, which causes African trypanosomiasis, avoids immunity by periodically switching its surface composition. The parasite is coated by 10 million... (Review)
Review
Trypanosoma brucei, which causes African trypanosomiasis, avoids immunity by periodically switching its surface composition. The parasite is coated by 10 million identical, monoallelically expressed variant surface glycoprotein (VSG) molecules. Multiple distinct parasites (with respect to their VSG coat) coexist simultaneously during each wave of parasitemia. This substantial antigenic load is countered by B cells whose antigen receptors (antibodies or immunoglobulins) are also monoallelically expressed, and that diversify dynamically to counter each variant antigen. Here we examine parallels between the processes that generate VSGs and antibodies. We also discuss current insights into VSG mRNA regulation that may inform the emerging field of Ig mRNA biology. We conclude by extending the parallels between VSG and Ig to the protein level.
Topics: Antibodies, Protozoan; Antigenic Variation; B-Lymphocytes; Humans; Trypanosoma brucei brucei; Trypanosomiasis, African
PubMed: 30826207
DOI: 10.1016/j.pt.2019.01.011 -
FEMS Microbiology Reviews Sep 2012Pathogenic microorganisms employ numerous molecular strategies in order to delay or circumvent recognition by the immune system of their host. One of the most widely... (Review)
Review
Pathogenic microorganisms employ numerous molecular strategies in order to delay or circumvent recognition by the immune system of their host. One of the most widely used strategies of immune evasion is antigenic variation, in which immunogenic molecules expressed on the surface of a microorganism are continuously modified. As a consequence, the host is forced to constantly adapt its humoral immune response against this pathogen. An antigenic change thus provides the microorganism with an opportunity to persist and/or replicate within the host (population) for an extended period of time or to effectively infect a previously infected host. In most cases, antigenic variation is caused by genetic processes that lead to the modification of the amino acid sequence of a particular antigen or to alterations in the expression of biosynthesis genes that induce changes in the expression of a variant antigen. Here, we will review antigenic variation systems that rely on homologous DNA recombination and that are found in a wide range of cellular, human pathogens, including bacteria (such as Neisseria spp., Borrelia spp., Treponema pallidum, and Mycoplasma spp.), fungi (such as Pneumocystis carinii) and parasites (such as the African trypanosome Trypanosoma brucei). Specifically, the various DNA recombination-based antigenic variation systems will be discussed with a focus on the employed mechanisms of recombination, the DNA substrates, and the enzymatic machinery involved.
Topics: Animals; Antigenic Variation; Bacteria; Host-Pathogen Interactions; Humans; Recombination, Genetic
PubMed: 22212019
DOI: 10.1111/j.1574-6976.2011.00321.x -
Research in Microbiology 1991Antigenic variation was demonstrated for the agent of relapsing fever, Borrelia hermsii. The phenomenon is correlated with changes in major surface proteins called Vmp.... (Review)
Review
Antigenic variation was demonstrated for the agent of relapsing fever, Borrelia hermsii. The phenomenon is correlated with changes in major surface proteins called Vmp. The genes encoding these antigens are located on linear plasmids. Expression occurs by transposition of genes encoding Vmp to a telomeric expression site located on another linear plasmid. Activation of a vmp gene occurs by placing it downstream from a promoter. Resemblance to the antigenic variation of trypanosomes is discussed.
Topics: Animals; Antigenic Variation; Blotting, Southern; Borrelia; Borrelia Infections; Humans; In Vitro Techniques; Membrane Proteins; Plasmids; Trypanosoma
PubMed: 1961981
DOI: 10.1016/0923-2508(91)90085-o -
Cell Apr 2002Cells often express only one gene from a set of two or more. African trypanosomes appear to accomplish this monoallelic expression by segregating the selected gene into... (Review)
Review
Cells often express only one gene from a set of two or more. African trypanosomes appear to accomplish this monoallelic expression by segregating the selected gene into a specific nuclear body. The possibility that such a structure might explain monoallelic expression in other multigene systems is discussed here.
Topics: Allelic Imbalance; Animals; Antigenic Variation; Cell Compartmentation; Cell Nucleus Structures; Gene Expression Regulation; Gene Silencing; Transcription, Genetic; Trypanosoma; Variant Surface Glycoproteins, Trypanosoma
PubMed: 11955440
DOI: 10.1016/s0092-8674(02)00711-0 -
Archives of Microbiology Mar 2021Mycoplasma pneumoniae and Mycoplasma genitalium are important causative agents of infections in humans. Like all other mycoplasmas, these species possess genomes that... (Review)
Review
Mycoplasma pneumoniae and Mycoplasma genitalium are important causative agents of infections in humans. Like all other mycoplasmas, these species possess genomes that are significantly smaller than that of other prokaryotes. Moreover, both organisms possess an exceptionally compact set of DNA recombination and repair-associated genes. These genes, however, are sufficient to generate antigenic variation by means of homologous recombination between specific repetitive genomic elements. At the same time, these mycoplasmas have likely evolved strategies to maintain the stability and integrity of their 'minimal' genomes. Previous studies have indicated that there are considerable differences between mycoplasmas and other bacteria in the composition of their DNA recombination and repair machinery. However, the complete repertoire of activities executed by the putative recombination and repair enzymes encoded by Mycoplasma species is not yet fully understood. In this paper, we review the current knowledge on the proteins that likely form part of the DNA repair and recombination pathways of two of the most clinically relevant Mycoplasma species, M. pneumoniae and M. genitalium. The characterization of these proteins will help to define the minimal enzymatic requirements for creating bacterial genetic diversity (antigenic variation) on the one hand, while maintaining genomic integrity on the other.
Topics: Antigenic Variation; DNA Repair; Gene Rearrangement; Genome, Bacterial; Genomics; Humans; Mycoplasma genitalium; Mycoplasma pneumoniae
PubMed: 32970220
DOI: 10.1007/s00203-020-02041-4 -
Veterinary Parasitology May 2006Babesia bovis and its bovine host interact in many ways, resulting in a range of disease and infection phenotypes. Host responses to the parasite elicit or select for a... (Comparative Study)
Comparative Study Review
Babesia bovis and its bovine host interact in many ways, resulting in a range of disease and infection phenotypes. Host responses to the parasite elicit or select for a variety of responses on the part of the parasite, the full range of which is not yet known. One well-established phenomenon, thought to aid parasite survival by evasion of host adaptive immune responses, is the sequential expansion of antigenically variant populations during an infection, a phenomenon referred to as "antigenic variation". Antigenic variation in B. bovis, like that in the human malarial parasite, Plasmodium falciparum, is intimately linked to a second survival mechanism, cytoadhesion. In cytoadhesion, mature parasite-containing erythrocytes bind to the capillary and post-capillary venous endothelium through parasite-derived ligands. The reliance of these parasites on both functions, and on their linkage, may provide opportunities to develop anti-babesial and, perhaps, anti-malarial protection strategies. The development of inhibitors of DNA metabolism in B. bovis may be used to abrogate the process of antigenic variation, whereas small molecular mimics may provide the means to vaccinate against a wide range of variants or to prevent the surface export of variant antigen ligands. In this article, aspects of antigenic variation and cytoadhesion in bovine babesiosis are explored, with a discussion of opportunities for prophylactic or therapeutic intervention in these intertwined processes.
Topics: Animals; Antigenic Variation; Antigens, Protozoan; Antigens, Surface; Babesia bovis; Babesiosis; Cell Adhesion; Mutation; Protozoan Proteins; Protozoan Vaccines
PubMed: 16517078
DOI: 10.1016/j.vetpar.2006.01.039