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An MPER antibody neutralizes HIV-1 using germline features shared among donors

The membrane-proximal external region (MPER) of HIV-1 envelope glycoprotein (Env) can be targeted by neutralizing antibodies of exceptional breadth. MPER antibodies usually have long, hydrophobic CDRH3s, lack activity as inferred germline precursors, are often from the minor IgG3 subclass, and some...

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Autores principales: Zhang, Lei, Irimia, Adriana, He, Lingling, Landais, Elise, Rantalainen, Kimmo, Leaman, Daniel P., Vollbrecht, Thomas, Stano, Armando, Sands, Daniel I., Kim, Arthur S., Poignard, Pascal, Burton, Dennis R., Murrell, Ben, Ward, Andrew B., Zhu, Jiang, Wilson, Ian A., Zwick, Michael B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879610/
https://www.ncbi.nlm.nih.gov/pubmed/31772165
http://dx.doi.org/10.1038/s41467-019-12973-1
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author Zhang, Lei
Irimia, Adriana
He, Lingling
Landais, Elise
Rantalainen, Kimmo
Leaman, Daniel P.
Vollbrecht, Thomas
Stano, Armando
Sands, Daniel I.
Kim, Arthur S.
Poignard, Pascal
Burton, Dennis R.
Murrell, Ben
Ward, Andrew B.
Zhu, Jiang
Wilson, Ian A.
Zwick, Michael B.
author_facet Zhang, Lei
Irimia, Adriana
He, Lingling
Landais, Elise
Rantalainen, Kimmo
Leaman, Daniel P.
Vollbrecht, Thomas
Stano, Armando
Sands, Daniel I.
Kim, Arthur S.
Poignard, Pascal
Burton, Dennis R.
Murrell, Ben
Ward, Andrew B.
Zhu, Jiang
Wilson, Ian A.
Zwick, Michael B.
author_sort Zhang, Lei
collection PubMed
description The membrane-proximal external region (MPER) of HIV-1 envelope glycoprotein (Env) can be targeted by neutralizing antibodies of exceptional breadth. MPER antibodies usually have long, hydrophobic CDRH3s, lack activity as inferred germline precursors, are often from the minor IgG3 subclass, and some are polyreactive, such as 4E10. Here we describe an MPER broadly neutralizing antibody from the major IgG1 subclass, PGZL1, which shares germline V/D-region genes with 4E10, has a shorter CDRH3, and is less polyreactive. A recombinant sublineage variant pan-neutralizes a 130-isolate panel at 1.4 μg/ml (IC(50)). Notably, a germline revertant with mature CDR3s neutralizes 12% of viruses and still binds MPER after DJ reversion. Crystal structures of lipid-bound PGZL1 variants and cryo-EM reconstruction of an Env-PGZL1 complex reveal how these antibodies recognize MPER and viral membrane. Discovery of common genetic and structural elements among MPER antibodies from different patients suggests that such antibodies could be elicited using carefully designed immunogens.
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spelling pubmed-68796102019-11-29 An MPER antibody neutralizes HIV-1 using germline features shared among donors Zhang, Lei Irimia, Adriana He, Lingling Landais, Elise Rantalainen, Kimmo Leaman, Daniel P. Vollbrecht, Thomas Stano, Armando Sands, Daniel I. Kim, Arthur S. Poignard, Pascal Burton, Dennis R. Murrell, Ben Ward, Andrew B. Zhu, Jiang Wilson, Ian A. Zwick, Michael B. Nat Commun Article The membrane-proximal external region (MPER) of HIV-1 envelope glycoprotein (Env) can be targeted by neutralizing antibodies of exceptional breadth. MPER antibodies usually have long, hydrophobic CDRH3s, lack activity as inferred germline precursors, are often from the minor IgG3 subclass, and some are polyreactive, such as 4E10. Here we describe an MPER broadly neutralizing antibody from the major IgG1 subclass, PGZL1, which shares germline V/D-region genes with 4E10, has a shorter CDRH3, and is less polyreactive. A recombinant sublineage variant pan-neutralizes a 130-isolate panel at 1.4 μg/ml (IC(50)). Notably, a germline revertant with mature CDR3s neutralizes 12% of viruses and still binds MPER after DJ reversion. Crystal structures of lipid-bound PGZL1 variants and cryo-EM reconstruction of an Env-PGZL1 complex reveal how these antibodies recognize MPER and viral membrane. Discovery of common genetic and structural elements among MPER antibodies from different patients suggests that such antibodies could be elicited using carefully designed immunogens. Nature Publishing Group UK 2019-11-26 /pmc/articles/PMC6879610/ /pubmed/31772165 http://dx.doi.org/10.1038/s41467-019-12973-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhang, Lei
Irimia, Adriana
He, Lingling
Landais, Elise
Rantalainen, Kimmo
Leaman, Daniel P.
Vollbrecht, Thomas
Stano, Armando
Sands, Daniel I.
Kim, Arthur S.
Poignard, Pascal
Burton, Dennis R.
Murrell, Ben
Ward, Andrew B.
Zhu, Jiang
Wilson, Ian A.
Zwick, Michael B.
An MPER antibody neutralizes HIV-1 using germline features shared among donors
title An MPER antibody neutralizes HIV-1 using germline features shared among donors
title_full An MPER antibody neutralizes HIV-1 using germline features shared among donors
title_fullStr An MPER antibody neutralizes HIV-1 using germline features shared among donors
title_full_unstemmed An MPER antibody neutralizes HIV-1 using germline features shared among donors
title_short An MPER antibody neutralizes HIV-1 using germline features shared among donors
title_sort mper antibody neutralizes hiv-1 using germline features shared among donors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879610/
https://www.ncbi.nlm.nih.gov/pubmed/31772165
http://dx.doi.org/10.1038/s41467-019-12973-1
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