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  • 1
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    A yeast-endonuclease-generated DNA break induces antigenic switching in Trypanosoma brucei (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-04-17
    Description: Trypanosoma brucei is the causative agent of African sleeping sickness in humans and one of the causes of nagana in cattle. This protozoan parasite evades the host immune system by antigenic variation, a periodic switching of its variant surface glycoprotein (VSG) coat. VSG switching is spontaneous and occurs at a rate of about 10(-2)-10(-3) per population doubling in recent isolates from nature, but at a markedly reduced rate (10(-5)-10(-6)) in laboratory-adapted strains. VSG switching is thought to occur predominantly through gene conversion, a form of homologous recombination initiated by a DNA lesion that is used by other pathogens (for example, Candida albicans, Borrelia sp. and Neisseria gonorrhoeae) to generate surface protein diversity, and by B lymphocytes of the vertebrate immune system to generate antibody diversity. Very little is known about the molecular mechanism of VSG switching in T. brucei. Here we demonstrate that the introduction of a DNA double-stranded break (DSB) adjacent to the approximately 70-base-pair (bp) repeats upstream of the transcribed VSG gene increases switching in vitro approximately 250-fold, producing switched clones with a frequency and features similar to those generated early in an infection. We were also able to detect spontaneous DSBs within the 70-bp repeats upstream of the actively transcribed VSG gene, indicating that a DSB is a natural intermediate of VSG gene conversion and that VSG switching is the result of the resolution of this DSB by break-induced replication.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688456/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688456/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boothroyd, Catharine E -- Dreesen, Oliver -- Leonova, Tatyana -- Ly, K Ina -- Figueiredo, Luisa M -- Cross, George A M -- Papavasiliou, F Nina -- R01 AI021729/AI/NIAID NIH HHS/ -- R01 AI021729-25/AI/NIAID NIH HHS/ -- R01 AI085973/AI/NIAID NIH HHS/ -- R01AI021729/AI/NIAID NIH HHS/ -- England -- Nature. 2009 May 14;459(7244):278-81. doi: 10.1038/nature07982. Epub 2009 Apr 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Lymphocyte Biology, The Rockefeller University, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19369939" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigenic Variation/*genetics ; *DNA Breaks, Double-Stranded ; DNA Repair/genetics ; DNA Replication ; Deoxyribonucleases, Type II Site-Specific/genetics/*metabolism ; Gene Conversion/genetics ; *Models, Genetic ; Polymerase Chain Reaction ; Saccharomyces cerevisiae/enzymology/genetics ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; Sequence Analysis ; Trypanosoma brucei brucei/*genetics/*immunology ; Variant Surface Glycoproteins, Trypanosoma/genetics/immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    The in vivo dynamics of antigenic variation in Trypanosoma brucei (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-03-31
    Description: Trypanosoma brucei, a causative agent of African Sleeping Sickness, constantly changes its dense variant surface glycoprotein (VSG) coat to avoid elimination by the immune system of its mammalian host, using an extensive repertoire of dedicated genes. However, the dynamics of VSG expression in T. brucei during an infection are poorly understood. We have developed a method, based on de novo assembly of VSGs, for quantitatively examining the diversity of expressed VSGs in any population of trypanosomes and monitored VSG population dynamics in vivo. Our experiments revealed unexpected diversity within parasite populations and a mechanism for diversifying the genome-encoded VSG repertoire. The interaction between T. brucei and its host is substantially more dynamic and nuanced than previously expected.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514441/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514441/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mugnier, Monica R -- Cross, George A M -- Papavasiliou, F Nina -- AI085973/AI/NIAID NIH HHS/ -- R01 AI085973/AI/NIAID NIH HHS/ -- R01 AI097127/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 27;347(6229):1470-3. doi: 10.1126/science.aaa4502.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Lymphocyte Biology, The Rockefeller University, New York, NY, USA. Laboratory of Molecular Parasitology, The Rockefeller University, New York, NY, USA. ; Laboratory of Lymphocyte Biology, The Rockefeller University, New York, NY, USA. Laboratory of Molecular Parasitology, The Rockefeller University, New York, NY, USA. papavasiliou@rockefeller.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25814582" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Antigenic Variation ; Host-Parasite Interactions/*immunology ; Humans ; Mice ; Mice, Inbred BALB C ; Trypanosoma brucei brucei/*immunology ; Trypanosomiasis, African/*immunology ; Variant Surface Glycoproteins, Trypanosoma/*immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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