The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody.

Immunogen design for HIV-1 vaccines could be based on epitope identification of naturally occurring neutralizing antibodies in infected patients. A tier 2 neutralizing monoclonal antibody (mAb), HJ16 recognizes a new epitope in the CD4 binding site (CD4bs) region that only partially overlaps with th...

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Autores principales:	Sunita S Balla-Jhagjhoorsingh, Davide Corti, Leo Heyndrickx, Elisabeth Willems, Katleen Vereecken, David Davis, Guido Vanham
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7f92aeb3878d4fa3843e47aaabbfeeb0
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spelling	oai:doaj.org-article:7f92aeb3878d4fa3843e47aaabbfeeb02021-11-18T07:37:22ZThe N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody.1932-620310.1371/journal.pone.0068863https://doaj.org/article/7f92aeb3878d4fa3843e47aaabbfeeb02013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23874792/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Immunogen design for HIV-1 vaccines could be based on epitope identification of naturally occurring neutralizing antibodies in infected patients. A tier 2 neutralizing monoclonal antibody (mAb), HJ16 recognizes a new epitope in the CD4 binding site (CD4bs) region that only partially overlaps with the b12 epitope. We aimed to identify the critical binding site by resistance induction in a sensitive primary CRF02_AG strain. In four independent dose-escalation studies, the N276D mutation was consistently the only alteration found and it was confirmed to be responsible for resistance to HJ16 by site-directed mutagenesis in envelopes (envs) of the homologous CRF02_AG, as well as of a subtype A and a subtype C primary isolate. This mutation removes an N-linked glycosylation site. The effect of N276D was very selective, as it failed to confer resistance to a range of other entry inhibitors. Remarkably, sensitivity to the CD4bs VRC01 and VRC03 mAbs was increased in the N276D mutated viruses. These data indicate that binding of the CD4bs specific HJ16 mAb critically depends on the interaction with the N276-glycan, thus indicating that HJ16 is the first glycan dependent CD4bs-specific mAb.Sunita S Balla-JhagjhoorsinghDavide CortiLeo HeyndrickxElisabeth WillemsKatleen VereeckenDavid DavisGuido VanhamPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e68863 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sunita S Balla-Jhagjhoorsingh Davide Corti Leo Heyndrickx Elisabeth Willems Katleen Vereecken David Davis Guido Vanham The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody.
description	Immunogen design for HIV-1 vaccines could be based on epitope identification of naturally occurring neutralizing antibodies in infected patients. A tier 2 neutralizing monoclonal antibody (mAb), HJ16 recognizes a new epitope in the CD4 binding site (CD4bs) region that only partially overlaps with the b12 epitope. We aimed to identify the critical binding site by resistance induction in a sensitive primary CRF02_AG strain. In four independent dose-escalation studies, the N276D mutation was consistently the only alteration found and it was confirmed to be responsible for resistance to HJ16 by site-directed mutagenesis in envelopes (envs) of the homologous CRF02_AG, as well as of a subtype A and a subtype C primary isolate. This mutation removes an N-linked glycosylation site. The effect of N276D was very selective, as it failed to confer resistance to a range of other entry inhibitors. Remarkably, sensitivity to the CD4bs VRC01 and VRC03 mAbs was increased in the N276D mutated viruses. These data indicate that binding of the CD4bs specific HJ16 mAb critically depends on the interaction with the N276-glycan, thus indicating that HJ16 is the first glycan dependent CD4bs-specific mAb.
format	article
author	Sunita S Balla-Jhagjhoorsingh Davide Corti Leo Heyndrickx Elisabeth Willems Katleen Vereecken David Davis Guido Vanham
author_facet	Sunita S Balla-Jhagjhoorsingh Davide Corti Leo Heyndrickx Elisabeth Willems Katleen Vereecken David Davis Guido Vanham
author_sort	Sunita S Balla-Jhagjhoorsingh
title	The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody.
title_short	The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody.
title_full	The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody.
title_fullStr	The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody.
title_full_unstemmed	The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody.
title_sort	n276 glycosylation site is required for hiv-1 neutralization by the cd4 binding site specific hj16 monoclonal antibody.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/7f92aeb3878d4fa3843e47aaabbfeeb0
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The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody.

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