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

Autor: Lee CD; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America., Watanabe Y; School of Biological Sciences, University of Southampton, Southampton, England, United Kingdom.; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, England, United Kingdom.; Division of Structural Biology, University of Oxford, Wellcome Centre for Human Genetics, Oxford, England, United Kingdom., Wu NC; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America., Han J; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America., Kumar S; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America., Pholcharee T; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America., Seabright GE; School of Biological Sciences, University of Southampton, Southampton, England, United Kingdom.; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, England, United Kingdom., Allen JD; School of Biological Sciences, University of Southampton, Southampton, England, United Kingdom., Lin CW; Department of Chemistry, The Scripps Research Institute, La Jolla, California, United States of America., Yang JR; Centers for Disease Control, Taipei City, Taiwan., Liu MT; Centers for Disease Control, Taipei City, Taiwan., Wu CY; Genomics Research Center, Academia Sinica, Taipei City, Taiwan., Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America., Crispin M; School of Biological Sciences, University of Southampton, Southampton, England, United Kingdom., Wilson IA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2021 Mar 22; Vol. 17 (3), pp. e1009407. Date of Electronic Publication: 2021 Mar 22 (Print Publication: 2021).
DOI: 10.1371/journal.ppat.1009407
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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