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Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development
HIV-1 broadly neutralizing antibodies (bnAbs) require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations for optimal neutralization potency. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infreque...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002614/ https://www.ncbi.nlm.nih.gov/pubmed/29861171 http://dx.doi.org/10.1016/j.chom.2018.04.018 |
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author | Wiehe, Kevin Bradley, Todd Meyerhoff, R. Ryan Hart, Connor Williams, Wilton B. Easterhoff, David Faison, William J. Kepler, Thomas B. Saunders, Kevin O. Alam, S. Munir Bonsignori, Mattia Haynes, Barton F. |
author_facet | Wiehe, Kevin Bradley, Todd Meyerhoff, R. Ryan Hart, Connor Williams, Wilton B. Easterhoff, David Faison, William J. Kepler, Thomas B. Saunders, Kevin O. Alam, S. Munir Bonsignori, Mattia Haynes, Barton F. |
author_sort | Wiehe, Kevin |
collection | PubMed |
description | HIV-1 broadly neutralizing antibodies (bnAbs) require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations for optimal neutralization potency. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infrequent. One bottleneck for induction of bnAbs is the evolution of viral envelopes (Envs) that can select bnAb B cell receptors (BCR) with improbable mutations. Here we define the probability of bnAb mutations and demonstrate the functional significance of key improbable mutations in three bnAb B cell lineages. We show that bnAbs are enriched for improbable mutations, which implies that their elicitation will be critical for successful vaccine induction of potent bnAb B cell lineages. We discuss a mutation-guided vaccine strategy for identification of Envs that can select B cells with BCRs that have key improbable mutations required for bnAb development. |
format | Online Article Text |
id | pubmed-6002614 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-60026142018-06-18 Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development Wiehe, Kevin Bradley, Todd Meyerhoff, R. Ryan Hart, Connor Williams, Wilton B. Easterhoff, David Faison, William J. Kepler, Thomas B. Saunders, Kevin O. Alam, S. Munir Bonsignori, Mattia Haynes, Barton F. Cell Host Microbe Article HIV-1 broadly neutralizing antibodies (bnAbs) require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations for optimal neutralization potency. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infrequent. One bottleneck for induction of bnAbs is the evolution of viral envelopes (Envs) that can select bnAb B cell receptors (BCR) with improbable mutations. Here we define the probability of bnAb mutations and demonstrate the functional significance of key improbable mutations in three bnAb B cell lineages. We show that bnAbs are enriched for improbable mutations, which implies that their elicitation will be critical for successful vaccine induction of potent bnAb B cell lineages. We discuss a mutation-guided vaccine strategy for identification of Envs that can select B cells with BCRs that have key improbable mutations required for bnAb development. Cell Press 2018-06-13 /pmc/articles/PMC6002614/ /pubmed/29861171 http://dx.doi.org/10.1016/j.chom.2018.04.018 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wiehe, Kevin Bradley, Todd Meyerhoff, R. Ryan Hart, Connor Williams, Wilton B. Easterhoff, David Faison, William J. Kepler, Thomas B. Saunders, Kevin O. Alam, S. Munir Bonsignori, Mattia Haynes, Barton F. Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development |
title | Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development |
title_full | Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development |
title_fullStr | Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development |
title_full_unstemmed | Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development |
title_short | Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development |
title_sort | functional relevance of improbable antibody mutations for hiv broadly neutralizing antibody development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002614/ https://www.ncbi.nlm.nih.gov/pubmed/29861171 http://dx.doi.org/10.1016/j.chom.2018.04.018 |
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