Antibody-Dependent Cellular Cytotoxicity against Reactivated HIV-1-Infected Cells.

Détails

ID Serval
serval:BIB_2E8C4C6F8EA3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Antibody-Dependent Cellular Cytotoxicity against Reactivated HIV-1-Infected Cells.
Périodique
Journal of virology
Auteur⸱e⸱s
Lee W.S., Richard J., Lichtfuss M., Smith A.B., Park J., Courter J.R., Melillo B.N., Sodroski J.G., Kaufmann D.E., Finzi A., Parsons M.S., Kent S.J.
ISSN
1098-5514 (Electronic)
ISSN-L
0022-538X
Statut éditorial
Publié
Date de publication
15/02/2016
Peer-reviewed
Oui
Volume
90
Numéro
4
Pages
2021-2030
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
Lifelong antiretroviral therapy (ART) for HIV-1 does not diminish the established latent reservoir. A possible cure approach is to reactivate the quiescent genome from latency and utilize immune responses to eliminate cells harboring reactivated HIV-1. It is not known whether antibodies within HIV-1-infected individuals can recognize and eliminate cells reactivated from latency through antibody-dependent cellular cytotoxicity (ADCC). We found that reactivation of HIV-1 expression in the latently infected ACH-2 cell line elicited antibody-mediated NK cell activation but did not result in antibody-mediated killing. The lack of CD4 expression on these HIV-1 envelope (Env)-expressing cells likely resulted in poor recognition of CD4-induced antibody epitopes on Env. To examine this further, cultured primary CD4(+) T cells from HIV-1(+) subjects were used as targets for ADCC. These ex vivo-expanded primary cells were modestly susceptible to ADCC mediated by autologous or heterologous HIV-1(+) serum antibodies. Importantly, ADCC mediated against these primary cells could be enhanced following incubation with a CD4-mimetic compound (JP-III-48) that exposes CD4-induced antibody epitopes on Env. Our studies suggest that with sufficient reactivation and expression of appropriate Env epitopes, primary HIV-1-infected cells can be targets for ADCC mediated by autologous serum antibodies and innate effector cells. The results of this study suggest that further investigation into the potential of ADCC to eliminate reactivated latently infected cells is warranted.
An HIV-1 cure remains elusive due to the persistence of long-lived latently infected cells. An HIV-1 cure strategy, termed "shock and kill," aims to reactivate HIV-1 expression in latently infected cells and subsequently eliminate the reactivated cells through immune-mediated killing. While recent research efforts have focused on reversing HIV-1 latency, it remains unclear whether preexisting immune responses within HIV-1(+) individuals can efficiently eliminate the reactivated cells. HIV-1-specific antibodies can potentially eliminate cells reactivated from latency via Fc effector functions by recruiting innate immune cells. Our study highlights the potential role that antibody-dependent cellular cytotoxicity might play in antilatency cure approaches.
Mots-clé
Adult, Antibody-Dependent Cell Cytotoxicity, CD4-Positive T-Lymphocytes/immunology, CD4-Positive T-Lymphocytes/virology, Cells, Cultured, HIV Antibodies/immunology, HIV-1/immunology, HIV-1/physiology, Humans, Male, Middle Aged, Virus Activation
Pubmed
Web of science
Open Access
Oui
Création de la notice
09/05/2023 12:59
Dernière modification de la notice
29/11/2024 16:54
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