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

Szojka, Zsófia Ilona LU ; Karlson, Sara LU orcid ; Johansson, Emil LU orcid ; Şahin, Gülşen Özkaya LU and Jansson, Marianne LU (2022) In International Journal of Molecular Sciences 23(9).
Abstract

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... (More)

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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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Env motifs, HIV-2, neutralization sensitivity, target cell co-receptors
in
International Journal of Molecular Sciences
volume
23
issue
9
article number
4766
publisher
MDPI AG
external identifiers
  • pmid:35563157
  • scopus:85128738879
ISSN
1661-6596
DOI
10.3390/ijms23094766
language
English
LU publication?
yes
id
7656105e-92d9-478c-b2ba-7192eda9cb53
date added to LUP
2022-06-30 14:43:17
date last changed
2025-10-14 11:32:48
@article{7656105e-92d9-478c-b2ba-7192eda9cb53,
  abstract     = {{<p>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.</p>}},
  author       = {{Szojka, Zsófia Ilona and Karlson, Sara and Johansson, Emil and Şahin, Gülşen Özkaya and Jansson, Marianne}},
  issn         = {{1661-6596}},
  keywords     = {{Env motifs; HIV-2; neutralization sensitivity; target cell co-receptors}},
  language     = {{eng}},
  number       = {{9}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{HIV-2 Neutralization Sensitivity in Relation to Co-Receptor Entry Pathways and Env Motifs}},
  url          = {{http://dx.doi.org/10.3390/ijms23094766}},
  doi          = {{10.3390/ijms23094766}},
  volume       = {{23}},
  year         = {{2022}},
}