Antibody neutralization and escape by HIV-1
Abstract
Neutralizing antibodies (Nab) are a principal component of an effective human immune response to many pathogens, yet their role in HIV-1 infection is unclear. To gain a better understanding of this role, we examined plasma from patients with acute HIV infection. Here we report the detection of autologous Nab as early as 52 days after detection of HIV-specific antibodies. The viral inhibitory activity of Nab resulted in complete replacement of neutralization-sensitive virus by successive populations of resistant virus. Escape virus contained mutations in the env gene that were unexpectedly sparse, did not map generally to known neutralization epitopes, and involved primarily changes in N-linked glycosylation. This pattern of escape, and the exceptional density of HIV-1 envelope glycosylation generally, led us to postulate an evolving 'glycan shield' mechanism of neutralization escape whereby selected changes in glycan packing prevent Nab binding but not receptor binding. Direct support for this model was obtained by mutational substitution showing that Nab-selected alterations in glycosylation conferred escape from both autologous antibody and epitope-specific monoclonal antibodies. The evolving glycan shield thus represents a new mechanism contributing to HIV-1 persistence in the face of an evolving antibody repertoire.
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HIV-1 Env contains ~25 glycosylation sites and forms a glycan shield protecting the virus from neutralizing antibodies; HTLV-1 Env contains only five sites for N-glycan attachment.
“Unlike HIV-1 Env, which contains ~25 glycosylation sites [101], and forms a “glycan shield” protecting the virus from neutralizing antibodies [102], HTLV-1 Env contains only five sites for N-glycan attachment [103].”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [102]
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“Unlike HIV-1 Env, which contains ~25 glycosylation sites [101], and forms a “glycan shield” protecting the virus from neutralizing antibodies [102], HTLV-1 Env contains only five sites for N-glycan attachment [103].”
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- Authors
- Wei, X., Decker, J. M., Wang, S., Hui, H., Kappes, J. C., Wu, X., Salazar-Gonzalez, J. F., Salazar, M. G., Kilby, J. M., Saag, M. S., Komarova, N. L., Nowak, M. A., Hahn, B. H., Kwong, P. D., & Shaw, G. M.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of Alabama at Birmingham (US)
- Institute for Advanced Study (US)
- National Institutes of Health (US)
- Corresponding author
- Shaw, George M.
- ORCID
- Venue
- Nature
- Published
- 2003-03-20
- Volume
- 422
- Issue
- 6929
- Pages
- 307-312
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1997677784
- Cited by
- 2,421
- References
- 0
- Citations by year
- 2026: 47 · 2025: 49 · 2024: 45 · 2023: 46 · 2022: 67 · 2021: 90 · 2020: 110 · 2019: 86 · 2018: 103 · 2017: 117 · 2016: 94 · 2015: 117 · 2014: 99 · 2013: 132 · 2012: 153
- FWCI
- 42.76
- Type
- journal article
- Language
- en
- Update notices
- erratum (2003-05-08)
- Open access
- closed
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Physical Sciences › Chemistry › Organic Chemistry › Carbohydrate Chemistry and Synthesis
- Keywords
- HIV-1, neutralizing antibodies, antibody escape, acute HIV infection, glycan shield, neutralizing epitopes, monoclonal antibodies, HIV-1 persistence
- MeSH terms
- Amino Acid Sequence, Antibodies, Monoclonal, Antibody Specificity, Epitopes, Glycosylation, Humans, Immune Sera, Models, Biological, Molecular Sequence Data, Neutralization Tests, Time Factors, HIV Antibodies, HIV Antigens, HIV-1, HIV Infections, HIV Envelope Protein gp120, HIV Envelope Protein gp41, CD4 Antigens, Mutagenesis
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