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Signal peptide of HIV-1 envelope modulates glycosylation impacting exposure of V1V2 and other epitopes
HIV-1 envelope (Env) is a trimer of gp120-gp41 heterodimers, synthesized from a precursor gp160 that contains an ER-targeting signal peptide (SP) at its amino-terminus. Each trimer is swathed by ~90 N-linked glycans, comprising complex-type and oligomannose-type glycans, which play an important role...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793277/ https://www.ncbi.nlm.nih.gov/pubmed/33370382 http://dx.doi.org/10.1371/journal.ppat.1009185 |
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author | Upadhyay, Chitra Feyznezhad, Roya Cao, Liwei Chan, Kun-Wei Liu, Kevin Yang, Weiming Zhang, Hui Yolitz, Jason Arthos, James Nadas, Arthur Kong, Xiang-Peng Zolla-Pazner, Susan Hioe, Catarina E. |
author_facet | Upadhyay, Chitra Feyznezhad, Roya Cao, Liwei Chan, Kun-Wei Liu, Kevin Yang, Weiming Zhang, Hui Yolitz, Jason Arthos, James Nadas, Arthur Kong, Xiang-Peng Zolla-Pazner, Susan Hioe, Catarina E. |
author_sort | Upadhyay, Chitra |
collection | PubMed |
description | HIV-1 envelope (Env) is a trimer of gp120-gp41 heterodimers, synthesized from a precursor gp160 that contains an ER-targeting signal peptide (SP) at its amino-terminus. Each trimer is swathed by ~90 N-linked glycans, comprising complex-type and oligomannose-type glycans, which play an important role in determining virus sensitivity to neutralizing antibodies. We previously examined the effects of single point SP mutations on Env properties and functions. Here, we aimed to understand the impact of the SP diversity on glycosylation of virus-derived Env and virus neutralization by swapping SPs. Analyses of site-specific glycans revealed that SP swapping altered Env glycan content and occupancy on multiple N-linked glycosites, including conserved N156 and N160 glycans in the V1V2 region at the Env trimer apex and N88 at the trimer base. Virus neutralization was also affected, especially by antibodies against V1V2, V3, and gp41. Likewise, SP swaps affected the recognition of soluble and cell-associated Env by antibodies targeting distinct V1V2 configurations, V3 crown, and gp41 epitopes. These data highlight the contribution of SP sequence diversity in shaping the Env glycan content and its impact on the configuration and accessibility of V1V2 and other Env epitopes. |
format | Online Article Text |
id | pubmed-7793277 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-77932772021-01-27 Signal peptide of HIV-1 envelope modulates glycosylation impacting exposure of V1V2 and other epitopes Upadhyay, Chitra Feyznezhad, Roya Cao, Liwei Chan, Kun-Wei Liu, Kevin Yang, Weiming Zhang, Hui Yolitz, Jason Arthos, James Nadas, Arthur Kong, Xiang-Peng Zolla-Pazner, Susan Hioe, Catarina E. PLoS Pathog Research Article HIV-1 envelope (Env) is a trimer of gp120-gp41 heterodimers, synthesized from a precursor gp160 that contains an ER-targeting signal peptide (SP) at its amino-terminus. Each trimer is swathed by ~90 N-linked glycans, comprising complex-type and oligomannose-type glycans, which play an important role in determining virus sensitivity to neutralizing antibodies. We previously examined the effects of single point SP mutations on Env properties and functions. Here, we aimed to understand the impact of the SP diversity on glycosylation of virus-derived Env and virus neutralization by swapping SPs. Analyses of site-specific glycans revealed that SP swapping altered Env glycan content and occupancy on multiple N-linked glycosites, including conserved N156 and N160 glycans in the V1V2 region at the Env trimer apex and N88 at the trimer base. Virus neutralization was also affected, especially by antibodies against V1V2, V3, and gp41. Likewise, SP swaps affected the recognition of soluble and cell-associated Env by antibodies targeting distinct V1V2 configurations, V3 crown, and gp41 epitopes. These data highlight the contribution of SP sequence diversity in shaping the Env glycan content and its impact on the configuration and accessibility of V1V2 and other Env epitopes. Public Library of Science 2020-12-28 /pmc/articles/PMC7793277/ /pubmed/33370382 http://dx.doi.org/10.1371/journal.ppat.1009185 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Upadhyay, Chitra Feyznezhad, Roya Cao, Liwei Chan, Kun-Wei Liu, Kevin Yang, Weiming Zhang, Hui Yolitz, Jason Arthos, James Nadas, Arthur Kong, Xiang-Peng Zolla-Pazner, Susan Hioe, Catarina E. Signal peptide of HIV-1 envelope modulates glycosylation impacting exposure of V1V2 and other epitopes |
title | Signal peptide of HIV-1 envelope modulates glycosylation impacting exposure of V1V2 and other epitopes |
title_full | Signal peptide of HIV-1 envelope modulates glycosylation impacting exposure of V1V2 and other epitopes |
title_fullStr | Signal peptide of HIV-1 envelope modulates glycosylation impacting exposure of V1V2 and other epitopes |
title_full_unstemmed | Signal peptide of HIV-1 envelope modulates glycosylation impacting exposure of V1V2 and other epitopes |
title_short | Signal peptide of HIV-1 envelope modulates glycosylation impacting exposure of V1V2 and other epitopes |
title_sort | signal peptide of hiv-1 envelope modulates glycosylation impacting exposure of v1v2 and other epitopes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793277/ https://www.ncbi.nlm.nih.gov/pubmed/33370382 http://dx.doi.org/10.1371/journal.ppat.1009185 |
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