Structure of the Lassa virus glycan shield provides a model for immunological resistance
Lassa virus is an Old World arenavirus endemic to West Africa that causes severe hemorrhagic fever. Vaccine development has focused on the envelope glycoprotein complex (GPC) that extends from the virion envelope. The often inadequate antibody immune response elicited by both vaccine and natural inf...
| Auteurs principaux: | , , , , , , , , , |
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| Format: | Journal article |
| Langue: | English |
| Publié: |
National Academy of Sciences
2018
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| _version_ | 1826270885898616832 |
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| author | Watanabe, Y Raghwani, j Allen, J Seabright, G Li, S Moser, F Huiskonen, J Strecker, T Bowden, T Crispin, M |
| author_facet | Watanabe, Y Raghwani, j Allen, J Seabright, G Li, S Moser, F Huiskonen, J Strecker, T Bowden, T Crispin, M |
| author_sort | Watanabe, Y |
| collection | OXFORD |
| description | Lassa virus is an Old World arenavirus endemic to West Africa that causes severe hemorrhagic fever. Vaccine development has focused on the envelope glycoprotein complex (GPC) that extends from the virion envelope. The often inadequate antibody immune response elicited by both vaccine and natural infection has been, in part, attributed to the abundance of N-linked glycosylation on the GPC. Here, using a virus-like-particle system that presents Lassa virus GPC in a native-like context, we determine the composite population of each of the N-linked glycosylation sites presented on the trimeric GPC spike. Our analysis reveals the presence of underprocessed oligomannose-type glycans, which form punctuated clusters that obscure the proteinous surface of both the GP1 attachment and GP2 fusion glycoprotein subunits of the Lassa virus GPC. These oligomannose clusters are seemingly derived as a result of sterically reduced accessibility to glycan processing enzymes, and limited amino acid diversification around these sites supports their role protecting against the humoral immune response. Combined, our data provide a structure-based blueprint for understanding how glycans render the glycoprotein spikes of Lassa virus and other Old World arenaviruses immunologically resistant targets. |
| first_indexed | 2024-03-06T21:47:53Z |
| format | Journal article |
| id | oxford-uuid:4a3a95c7-495a-4c21-b11d-d171350aeb56 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:47:53Z |
| publishDate | 2018 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | oxford-uuid:4a3a95c7-495a-4c21-b11d-d171350aeb562022-03-26T15:36:22ZStructure of the Lassa virus glycan shield provides a model for immunological resistanceJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4a3a95c7-495a-4c21-b11d-d171350aeb56EnglishSymplectic Elements at OxfordNational Academy of Sciences2018Watanabe, YRaghwani, jAllen, JSeabright, GLi, SMoser, FHuiskonen, JStrecker, TBowden, TCrispin, MLassa virus is an Old World arenavirus endemic to West Africa that causes severe hemorrhagic fever. Vaccine development has focused on the envelope glycoprotein complex (GPC) that extends from the virion envelope. The often inadequate antibody immune response elicited by both vaccine and natural infection has been, in part, attributed to the abundance of N-linked glycosylation on the GPC. Here, using a virus-like-particle system that presents Lassa virus GPC in a native-like context, we determine the composite population of each of the N-linked glycosylation sites presented on the trimeric GPC spike. Our analysis reveals the presence of underprocessed oligomannose-type glycans, which form punctuated clusters that obscure the proteinous surface of both the GP1 attachment and GP2 fusion glycoprotein subunits of the Lassa virus GPC. These oligomannose clusters are seemingly derived as a result of sterically reduced accessibility to glycan processing enzymes, and limited amino acid diversification around these sites supports their role protecting against the humoral immune response. Combined, our data provide a structure-based blueprint for understanding how glycans render the glycoprotein spikes of Lassa virus and other Old World arenaviruses immunologically resistant targets. |
| spellingShingle | Watanabe, Y Raghwani, j Allen, J Seabright, G Li, S Moser, F Huiskonen, J Strecker, T Bowden, T Crispin, M Structure of the Lassa virus glycan shield provides a model for immunological resistance |
| title | Structure of the Lassa virus glycan shield provides a model for immunological resistance |
| title_full | Structure of the Lassa virus glycan shield provides a model for immunological resistance |
| title_fullStr | Structure of the Lassa virus glycan shield provides a model for immunological resistance |
| title_full_unstemmed | Structure of the Lassa virus glycan shield provides a model for immunological resistance |
| title_short | Structure of the Lassa virus glycan shield provides a model for immunological resistance |
| title_sort | structure of the lassa virus glycan shield provides a model for immunological resistance |
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