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A cross-neutralizing antibody between HIV-1 and influenza virus

A cross-neutralizing antibody between HIV-1 and influenza virus
A cross-neutralizing antibody between HIV-1 and influenza virus

Incessant antigenic evolution enables the persistence and spread of influenza virus in the human population. As the principal target of the immune response, the hemagglutinin (HA) surface antigen on influenza viruses continuously acquires and replaces N-linked glycosylation sites to shield immunogenic protein epitopes using host-derived glycans. Anti-glycan antibodies, such as 2G12, target the HIV-1 envelope protein (Env), which is even more extensively glycosylated and contains under-processed oligomannose-type clusters on its dense glycan shield. Here, we illustrate that 2G12 can also neutralize human seasonal influenza A H3N2 viruses that have evolved to present similar oligomannose-type clusters on their HAs from around 20 years after the 1968 pandemic. Using structural biology and mass spectrometric approaches, we find that two N-glycosylation sites close to the receptor binding site (RBS) on influenza hemagglutinin represent the oligomannose cluster recognized by 2G12. One of these glycan sites is highly conserved in all human H3N2 strains and the other emerged during virus evolution. These two N-glycosylation sites have also become crucial for fitness of recent H3N2 strains. These findings shed light on the evolution of the glycan shield on influenza virus and suggest 2G12-like antibodies can potentially act as broad neutralizers to target human enveloped viruses.

1553-7366
Lee, Chang-Chun D
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Watanabe, Yasunori
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Wu, Nicholas C
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Han, Julianna
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Kumar, Sonu
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Pholcharee, Tossapol
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Seabright, Gemma E
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Allen, Joel D
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Lin, Chih-Wei
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Yang, Ji-Rong
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Liu, Ming-Tsan
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Wu, Chung-Yi
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Ward, Andrew B
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Crispin, Max
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Wilson, Ian A
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Lee, Chang-Chun D
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Watanabe, Yasunori
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Wu, Nicholas C
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Han, Julianna
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Kumar, Sonu
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Pholcharee, Tossapol
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Seabright, Gemma E
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Allen, Joel D
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Lin, Chih-Wei
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Yang, Ji-Rong
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Liu, Ming-Tsan
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Wu, Chung-Yi
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Ward, Andrew B
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Crispin, Max
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Wilson, Ian A
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Lee, Chang-Chun D, Watanabe, Yasunori, Wu, Nicholas C, Han, Julianna, Kumar, Sonu, Pholcharee, Tossapol, Seabright, Gemma E, Allen, Joel D, Lin, Chih-Wei, Yang, Ji-Rong, Liu, Ming-Tsan, Wu, Chung-Yi, Ward, Andrew B, Crispin, Max and Wilson, Ian A (2021) A cross-neutralizing antibody between HIV-1 and influenza virus. PLOS Pathogens, 17 (3), [1009407]. (doi:10.1371/journal.ppat.1009407).

Record type: Article

Abstract

Incessant antigenic evolution enables the persistence and spread of influenza virus in the human population. As the principal target of the immune response, the hemagglutinin (HA) surface antigen on influenza viruses continuously acquires and replaces N-linked glycosylation sites to shield immunogenic protein epitopes using host-derived glycans. Anti-glycan antibodies, such as 2G12, target the HIV-1 envelope protein (Env), which is even more extensively glycosylated and contains under-processed oligomannose-type clusters on its dense glycan shield. Here, we illustrate that 2G12 can also neutralize human seasonal influenza A H3N2 viruses that have evolved to present similar oligomannose-type clusters on their HAs from around 20 years after the 1968 pandemic. Using structural biology and mass spectrometric approaches, we find that two N-glycosylation sites close to the receptor binding site (RBS) on influenza hemagglutinin represent the oligomannose cluster recognized by 2G12. One of these glycan sites is highly conserved in all human H3N2 strains and the other emerged during virus evolution. These two N-glycosylation sites have also become crucial for fitness of recent H3N2 strains. These findings shed light on the evolution of the glycan shield on influenza virus and suggest 2G12-like antibodies can potentially act as broad neutralizers to target human enveloped viruses.

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journal.ppat.1009407 - Version of Record
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More information

Accepted/In Press date: 17 February 2021
e-pub ahead of print date: 22 March 2021
Published date: 22 March 2021
Additional Information: Publisher Copyright: © 2021 Public Library of Science. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

Identifiers

Local EPrints ID: 448966
URI: http://eprints.soton.ac.uk/id/eprint/448966
ISSN: 1553-7366
PURE UUID: fc129df5-d56c-4124-9b1d-0328ac586208
ORCID for Joel D Allen: ORCID iD orcid.org/0000-0003-2547-968X
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

Catalogue record

Date deposited: 12 May 2021 16:31
Last modified: 17 Mar 2024 04:09

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Contributors

Author: Chang-Chun D Lee
Author: Yasunori Watanabe
Author: Nicholas C Wu
Author: Julianna Han
Author: Sonu Kumar
Author: Tossapol Pholcharee
Author: Gemma E Seabright
Author: Joel D Allen ORCID iD
Author: Chih-Wei Lin
Author: Ji-Rong Yang
Author: Ming-Tsan Liu
Author: Chung-Yi Wu
Author: Andrew B Ward
Author: Max Crispin ORCID iD
Author: Ian A Wilson

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