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HIV-2 Neutralization Sensitivity in Relation to Co-Receptor Entry Pathways and Env Motifs

HIV-2, compared to HIV-1, elicits potent and broadly neutralizing antibodies, and uses a broad range of co-receptors. However, both sensitivity to neutralization and breadth of co-receptor use varies between HIV-2 isolates, and the molecular background is still not fully understood. Thus, in the cur...

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Autores principales: Szojka, Zsófia Ilona, Karlson, Sara, Johansson, Emil, Şahin, Gülşen Özkaya, Jansson, Marianne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9101540/
https://www.ncbi.nlm.nih.gov/pubmed/35563157
http://dx.doi.org/10.3390/ijms23094766
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author Szojka, Zsófia Ilona
Karlson, Sara
Johansson, Emil
Şahin, Gülşen Özkaya
Jansson, Marianne
author_facet Szojka, Zsófia Ilona
Karlson, Sara
Johansson, Emil
Şahin, Gülşen Özkaya
Jansson, Marianne
author_sort Szojka, Zsófia Ilona
collection PubMed
description HIV-2, compared to HIV-1, elicits potent and broadly neutralizing antibodies, and uses a broad range of co-receptors. However, both sensitivity to neutralization and breadth of co-receptor use varies between HIV-2 isolates, and the molecular background is still not fully understood. Thus, in the current study, we have deciphered relationships between HIV-2 neutralization sensitivity, co-receptor use and viral envelope glycoprotein (Env) molecular motifs. A panel of primary HIV-2 isolates, with predefined use of co-receptors, was assessed for neutralization sensitivity using a set of HIV-2 Env-directed monoclonal antibodies and co-receptor indicator cell lines. Neutralization sensitivity of the isolates was analysed in relation target cell co-receptor expression, in addition to amino acid motifs and predicted structures of Env regions. Results showed that HIV-2 isolates were more resistant to neutralizing antibodies when entering target cells via the alternative co-receptor GPR15, as compared to CCR5. A similar pattern was noted for isolates using the alternative co-receptor CXCR6. Sensitivity to neutralizing antibodies appeared also to be linked to specific Env motifs in V1/V2 and C3 regions. Our findings suggest that HIV-2 sensitivity to neutralization depends both on which co-receptor is used for cell entry and on specific Env motifs. This study highlights the multifactorial mechanisms behind HIV-2 neutralization sensitivity.
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spelling pubmed-91015402022-05-14 HIV-2 Neutralization Sensitivity in Relation to Co-Receptor Entry Pathways and Env Motifs Szojka, Zsófia Ilona Karlson, Sara Johansson, Emil Şahin, Gülşen Özkaya Jansson, Marianne Int J Mol Sci Article HIV-2, compared to HIV-1, elicits potent and broadly neutralizing antibodies, and uses a broad range of co-receptors. However, both sensitivity to neutralization and breadth of co-receptor use varies between HIV-2 isolates, and the molecular background is still not fully understood. Thus, in the current study, we have deciphered relationships between HIV-2 neutralization sensitivity, co-receptor use and viral envelope glycoprotein (Env) molecular motifs. A panel of primary HIV-2 isolates, with predefined use of co-receptors, was assessed for neutralization sensitivity using a set of HIV-2 Env-directed monoclonal antibodies and co-receptor indicator cell lines. Neutralization sensitivity of the isolates was analysed in relation target cell co-receptor expression, in addition to amino acid motifs and predicted structures of Env regions. Results showed that HIV-2 isolates were more resistant to neutralizing antibodies when entering target cells via the alternative co-receptor GPR15, as compared to CCR5. A similar pattern was noted for isolates using the alternative co-receptor CXCR6. Sensitivity to neutralizing antibodies appeared also to be linked to specific Env motifs in V1/V2 and C3 regions. Our findings suggest that HIV-2 sensitivity to neutralization depends both on which co-receptor is used for cell entry and on specific Env motifs. This study highlights the multifactorial mechanisms behind HIV-2 neutralization sensitivity. MDPI 2022-04-26 /pmc/articles/PMC9101540/ /pubmed/35563157 http://dx.doi.org/10.3390/ijms23094766 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Szojka, Zsófia Ilona
Karlson, Sara
Johansson, Emil
Şahin, Gülşen Özkaya
Jansson, Marianne
HIV-2 Neutralization Sensitivity in Relation to Co-Receptor Entry Pathways and Env Motifs
title HIV-2 Neutralization Sensitivity in Relation to Co-Receptor Entry Pathways and Env Motifs
title_full HIV-2 Neutralization Sensitivity in Relation to Co-Receptor Entry Pathways and Env Motifs
title_fullStr HIV-2 Neutralization Sensitivity in Relation to Co-Receptor Entry Pathways and Env Motifs
title_full_unstemmed HIV-2 Neutralization Sensitivity in Relation to Co-Receptor Entry Pathways and Env Motifs
title_short HIV-2 Neutralization Sensitivity in Relation to Co-Receptor Entry Pathways and Env Motifs
title_sort hiv-2 neutralization sensitivity in relation to co-receptor entry pathways and env motifs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9101540/
https://www.ncbi.nlm.nih.gov/pubmed/35563157
http://dx.doi.org/10.3390/ijms23094766
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