HIV-1 Envelope Glycoprotein Cell Surface Localization Is Associated with Antibody-Induced Internalization
To minimize immune responses against infected cells, HIV-1 has evolved different mechanisms to limit the surface expression of its envelope glycoproteins (Env). Recent observations suggest that the binding of certain broadly neutralizing antibodies (bNAbs) targeting the ‘closed’ conformation of Env...
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| Language: | English |
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MDPI AG
2021-09-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/10/1953 |
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| author | Sai Priya Anand Jérémie Prévost Jade Descôteaux-Dinelle Jonathan Richard Dung N. Nguyen Halima Medjahed Hung-Ching Chen Amos B. Smith Marzena Pazgier Andrés Finzi |
| author_facet | Sai Priya Anand Jérémie Prévost Jade Descôteaux-Dinelle Jonathan Richard Dung N. Nguyen Halima Medjahed Hung-Ching Chen Amos B. Smith Marzena Pazgier Andrés Finzi |
| author_sort | Sai Priya Anand |
| collection | DOAJ |
| description | To minimize immune responses against infected cells, HIV-1 has evolved different mechanisms to limit the surface expression of its envelope glycoproteins (Env). Recent observations suggest that the binding of certain broadly neutralizing antibodies (bNAbs) targeting the ‘closed’ conformation of Env induces its internalization. On the other hand, non-neutralizing antibodies (nNAbs) that preferentially target Env in its ‘open’ conformation, remain bound to Env on the cell surface for longer periods of time. In this study, we attempt to better understand the underlying mechanisms behind the differential rates of antibody-mediated Env internalization. We demonstrate that ‘forcing’ open Env using CD4 mimetics allows for nNAb binding and results in similar rates of Env internalization as those observed upon the bNAb binding. Moreover, we can identify distinct populations of Env that are differentially targeted by Abs that mediate faster rates of internalization, suggesting that the mechanism of antibody-induced Env internalization partially depends on the localization of Env on the cell surface. |
| first_indexed | 2024-03-10T06:08:42Z |
| format | Article |
| id | doaj.art-a5c2b75c440848ce9d22074a8844e5be |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T06:08:42Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-a5c2b75c440848ce9d22074a8844e5be2023-11-22T20:18:33ZengMDPI AGViruses1999-49152021-09-011310195310.3390/v13101953HIV-1 Envelope Glycoprotein Cell Surface Localization Is Associated with Antibody-Induced InternalizationSai Priya Anand0Jérémie Prévost1Jade Descôteaux-Dinelle2Jonathan Richard3Dung N. Nguyen4Halima Medjahed5Hung-Ching Chen6Amos B. Smith7Marzena Pazgier8Andrés Finzi9Centre de Recherche du CHUM, Montreal, QC H2X 0A9, CanadaCentre de Recherche du CHUM, Montreal, QC H2X 0A9, CanadaCentre de Recherche du CHUM, Montreal, QC H2X 0A9, CanadaCentre de Recherche du CHUM, Montreal, QC H2X 0A9, CanadaInfectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USACentre de Recherche du CHUM, Montreal, QC H2X 0A9, CanadaDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USAInfectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USACentre de Recherche du CHUM, Montreal, QC H2X 0A9, CanadaTo minimize immune responses against infected cells, HIV-1 has evolved different mechanisms to limit the surface expression of its envelope glycoproteins (Env). Recent observations suggest that the binding of certain broadly neutralizing antibodies (bNAbs) targeting the ‘closed’ conformation of Env induces its internalization. On the other hand, non-neutralizing antibodies (nNAbs) that preferentially target Env in its ‘open’ conformation, remain bound to Env on the cell surface for longer periods of time. In this study, we attempt to better understand the underlying mechanisms behind the differential rates of antibody-mediated Env internalization. We demonstrate that ‘forcing’ open Env using CD4 mimetics allows for nNAb binding and results in similar rates of Env internalization as those observed upon the bNAb binding. Moreover, we can identify distinct populations of Env that are differentially targeted by Abs that mediate faster rates of internalization, suggesting that the mechanism of antibody-induced Env internalization partially depends on the localization of Env on the cell surface.https://www.mdpi.com/1999-4915/13/10/1953HIV-1non-neutralizing antibodiesbroadly neutralizing antibodiesEnvinternalizationendocytosis |
| spellingShingle | Sai Priya Anand Jérémie Prévost Jade Descôteaux-Dinelle Jonathan Richard Dung N. Nguyen Halima Medjahed Hung-Ching Chen Amos B. Smith Marzena Pazgier Andrés Finzi HIV-1 Envelope Glycoprotein Cell Surface Localization Is Associated with Antibody-Induced Internalization Viruses HIV-1 non-neutralizing antibodies broadly neutralizing antibodies Env internalization endocytosis |
| title | HIV-1 Envelope Glycoprotein Cell Surface Localization Is Associated with Antibody-Induced Internalization |
| title_full | HIV-1 Envelope Glycoprotein Cell Surface Localization Is Associated with Antibody-Induced Internalization |
| title_fullStr | HIV-1 Envelope Glycoprotein Cell Surface Localization Is Associated with Antibody-Induced Internalization |
| title_full_unstemmed | HIV-1 Envelope Glycoprotein Cell Surface Localization Is Associated with Antibody-Induced Internalization |
| title_short | HIV-1 Envelope Glycoprotein Cell Surface Localization Is Associated with Antibody-Induced Internalization |
| title_sort | hiv 1 envelope glycoprotein cell surface localization is associated with antibody induced internalization |
| topic | HIV-1 non-neutralizing antibodies broadly neutralizing antibodies Env internalization endocytosis |
| url | https://www.mdpi.com/1999-4915/13/10/1953 |
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