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...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-04-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/9/4766 |
| _version_ | 1797504541579542528 |
|---|---|
| author | Zsófia Ilona Szojka Sara Karlson Emil Johansson Gülşen Özkaya Şahin Marianne Jansson |
| author_facet | Zsófia Ilona Szojka Sara Karlson Emil Johansson Gülşen Özkaya Şahin Marianne Jansson |
| author_sort | Zsófia Ilona Szojka |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T04:06:03Z |
| format | Article |
| id | doaj.art-3c58baa7d0ad4cc696e38454fb8f22ba |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:06:03Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3c58baa7d0ad4cc696e38454fb8f22ba2023-11-23T08:21:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01239476610.3390/ijms23094766HIV-2 Neutralization Sensitivity in Relation to Co-Receptor Entry Pathways and Env MotifsZsófia Ilona Szojka0Sara Karlson1Emil Johansson2Gülşen Özkaya Şahin3Marianne Jansson4Department of Laboratory Medicine, Lund University, 221 84 Lund, SwedenDepartment of Laboratory Medicine, Lund University, 221 84 Lund, SwedenDepartment of Laboratory Medicine, Lund University, 221 84 Lund, SwedenDepartment of Translational Medicine, Lund University, 205 02 Malmö, SwedenDepartment of Laboratory Medicine, Lund University, 221 84 Lund, SwedenHIV-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.https://www.mdpi.com/1422-0067/23/9/4766HIV-2neutralization sensitivitytarget cell co-receptorsEnv motifs |
| spellingShingle | Zsófia Ilona Szojka Sara Karlson Emil Johansson Gülşen Özkaya Şahin Marianne Jansson HIV-2 Neutralization Sensitivity in Relation to Co-Receptor Entry Pathways and Env Motifs International Journal of Molecular Sciences HIV-2 neutralization sensitivity target cell co-receptors 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 | HIV-2 neutralization sensitivity target cell co-receptors Env motifs |
| url | https://www.mdpi.com/1422-0067/23/9/4766 |
| work_keys_str_mv | AT zsofiailonaszojka hiv2neutralizationsensitivityinrelationtocoreceptorentrypathwaysandenvmotifs AT sarakarlson hiv2neutralizationsensitivityinrelationtocoreceptorentrypathwaysandenvmotifs AT emiljohansson hiv2neutralizationsensitivityinrelationtocoreceptorentrypathwaysandenvmotifs AT gulsenozkayasahin hiv2neutralizationsensitivityinrelationtocoreceptorentrypathwaysandenvmotifs AT mariannejansson hiv2neutralizationsensitivityinrelationtocoreceptorentrypathwaysandenvmotifs |