VSGs Expressed during Natural T. b. gambiense Infection Exhibit Extensive Sequence Divergence and a Subspecies-Specific Bias towards Type B N-Terminal Domains
ABSTRACT Trypanosoma brucei gambiense is the primary causative agent of human African trypanosomiasis (HAT), a vector-borne disease endemic to West and Central Africa. The extracellular parasite evades antibody recognition within the host bloodstream by altering its variant surface glycoprotein (VSG...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-12-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.02553-22 |
| _version_ | 1811289931957403648 |
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| author | Jaime So Sarah Sudlow Abeer Sayeed Tanner Grudda Stijn Deborggraeve Dieudonné Mumba Ngoyi Didier Kashiama Desamber Bill Wickstead Veerle Lejon Monica R. Mugnier |
| author_facet | Jaime So Sarah Sudlow Abeer Sayeed Tanner Grudda Stijn Deborggraeve Dieudonné Mumba Ngoyi Didier Kashiama Desamber Bill Wickstead Veerle Lejon Monica R. Mugnier |
| author_sort | Jaime So |
| collection | DOAJ |
| description | ABSTRACT Trypanosoma brucei gambiense is the primary causative agent of human African trypanosomiasis (HAT), a vector-borne disease endemic to West and Central Africa. The extracellular parasite evades antibody recognition within the host bloodstream by altering its variant surface glycoprotein (VSG) coat through a process of antigenic variation. The serological tests that are widely used to screen for HAT use VSG as one of the target antigens. However, the VSGs expressed during human infection have not been characterized. Here, we use VSG sequencing (VSG-seq) to analyze the VSGs expressed in the blood of patients infected with T. b. gambiense and compared them to VSG expression in Trypanosoma brucei rhodesiense infections in humans as well as Trypanosoma brucei brucei infections in mice. The 44 VSGs expressed during T. b. gambiense infection revealed a striking bias toward expression of type B N termini (82% of detected VSGs). This bias is specific to T. b. gambiense, which is unique among T. brucei subspecies in its chronic clinical presentation and anthroponotic nature. The expressed T. b. gambiense VSGs also share very little similarity to sequences from 36 T. b. gambiense whole-genome sequencing data sets, particularly in areas of the VSG protein exposed to host antibodies, suggesting the antigen repertoire is under strong selective pressure to diversify. Overall, this work demonstrates new features of antigenic variation in T. brucei gambiense and highlights the importance of understanding VSG repertoires in nature. IMPORTANCE Human African trypanosomiasis is a neglected tropical disease primarily caused by the extracellular parasite Trypanosoma brucei gambiense. To avoid elimination by the host, these parasites repeatedly replace their variant surface glycoprotein (VSG) coat. Despite the important role of VSGs in prolonging infection, VSG expression during human infections is poorly understood. A better understanding of natural VSG gene expression dynamics can clarify the mechanisms that T. brucei uses to alter its VSG coat. We analyzed the expressed VSGs detected in the blood of patients with trypanosomiasis. Our findings indicate that there are features of antigenic variation unique to human-infective T. brucei subspecies and that natural VSG repertoires may vary more than previously expected. |
| first_indexed | 2024-04-13T04:03:59Z |
| format | Article |
| id | doaj.art-0554be76d99843de9dd2daf7e05c92a2 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-04-13T04:03:59Z |
| publishDate | 2022-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-0554be76d99843de9dd2daf7e05c92a22022-12-22T03:03:23ZengAmerican Society for MicrobiologymBio2150-75112022-12-0113610.1128/mbio.02553-22VSGs Expressed during Natural T. b. gambiense Infection Exhibit Extensive Sequence Divergence and a Subspecies-Specific Bias towards Type B N-Terminal DomainsJaime So0Sarah Sudlow1Abeer Sayeed2Tanner Grudda3Stijn Deborggraeve4Dieudonné Mumba Ngoyi5Didier Kashiama Desamber6Bill Wickstead7Veerle Lejon8Monica R. Mugnier9Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USADepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USADepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USADepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USADepartment of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, BelgiumDepartment of Parasitology, Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the CongoProgramme Nationale de Lutte contre la Trypanosomiase Humaine Africaine (PNLTHA), Ministry of Health, Kinshasa, Democratic Republic of the CongoSchool of Life Sciences, Queen’s Medical Centre, University of Nottingham, Nottingham, United KingdomUMR-177 Intertryp, Institut de Recherche pour le Développement, Centre de Coopération Internationale en Recherche Agronomique pour le Développement, University of Montpellier, Montpellier, FranceDepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USAABSTRACT Trypanosoma brucei gambiense is the primary causative agent of human African trypanosomiasis (HAT), a vector-borne disease endemic to West and Central Africa. The extracellular parasite evades antibody recognition within the host bloodstream by altering its variant surface glycoprotein (VSG) coat through a process of antigenic variation. The serological tests that are widely used to screen for HAT use VSG as one of the target antigens. However, the VSGs expressed during human infection have not been characterized. Here, we use VSG sequencing (VSG-seq) to analyze the VSGs expressed in the blood of patients infected with T. b. gambiense and compared them to VSG expression in Trypanosoma brucei rhodesiense infections in humans as well as Trypanosoma brucei brucei infections in mice. The 44 VSGs expressed during T. b. gambiense infection revealed a striking bias toward expression of type B N termini (82% of detected VSGs). This bias is specific to T. b. gambiense, which is unique among T. brucei subspecies in its chronic clinical presentation and anthroponotic nature. The expressed T. b. gambiense VSGs also share very little similarity to sequences from 36 T. b. gambiense whole-genome sequencing data sets, particularly in areas of the VSG protein exposed to host antibodies, suggesting the antigen repertoire is under strong selective pressure to diversify. Overall, this work demonstrates new features of antigenic variation in T. brucei gambiense and highlights the importance of understanding VSG repertoires in nature. IMPORTANCE Human African trypanosomiasis is a neglected tropical disease primarily caused by the extracellular parasite Trypanosoma brucei gambiense. To avoid elimination by the host, these parasites repeatedly replace their variant surface glycoprotein (VSG) coat. Despite the important role of VSGs in prolonging infection, VSG expression during human infections is poorly understood. A better understanding of natural VSG gene expression dynamics can clarify the mechanisms that T. brucei uses to alter its VSG coat. We analyzed the expressed VSGs detected in the blood of patients with trypanosomiasis. Our findings indicate that there are features of antigenic variation unique to human-infective T. brucei subspecies and that natural VSG repertoires may vary more than previously expected.https://journals.asm.org/doi/10.1128/mbio.02553-22Trypanosomaantigenic variationgenomicshost-pathogen interactionsvariant surface glycoprotein |
| spellingShingle | Jaime So Sarah Sudlow Abeer Sayeed Tanner Grudda Stijn Deborggraeve Dieudonné Mumba Ngoyi Didier Kashiama Desamber Bill Wickstead Veerle Lejon Monica R. Mugnier VSGs Expressed during Natural T. b. gambiense Infection Exhibit Extensive Sequence Divergence and a Subspecies-Specific Bias towards Type B N-Terminal Domains mBio Trypanosoma antigenic variation genomics host-pathogen interactions variant surface glycoprotein |
| title | VSGs Expressed during Natural T. b. gambiense Infection Exhibit Extensive Sequence Divergence and a Subspecies-Specific Bias towards Type B N-Terminal Domains |
| title_full | VSGs Expressed during Natural T. b. gambiense Infection Exhibit Extensive Sequence Divergence and a Subspecies-Specific Bias towards Type B N-Terminal Domains |
| title_fullStr | VSGs Expressed during Natural T. b. gambiense Infection Exhibit Extensive Sequence Divergence and a Subspecies-Specific Bias towards Type B N-Terminal Domains |
| title_full_unstemmed | VSGs Expressed during Natural T. b. gambiense Infection Exhibit Extensive Sequence Divergence and a Subspecies-Specific Bias towards Type B N-Terminal Domains |
| title_short | VSGs Expressed during Natural T. b. gambiense Infection Exhibit Extensive Sequence Divergence and a Subspecies-Specific Bias towards Type B N-Terminal Domains |
| title_sort | vsgs expressed during natural t b gambiense infection exhibit extensive sequence divergence and a subspecies specific bias towards type b n terminal domains |
| topic | Trypanosoma antigenic variation genomics host-pathogen interactions variant surface glycoprotein |
| url | https://journals.asm.org/doi/10.1128/mbio.02553-22 |
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