PD-1 blockade potentiates HIV latency reversal ex vivo in CD4<sup>+</sup> T cells from ART-suppressed individuals.

Details

Serval ID
serval:BIB_3CB01C4A8D69
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
PD-1 blockade potentiates HIV latency reversal ex vivo in CD4<sup>+</sup> T cells from ART-suppressed individuals.
Journal
Nature communications
Author(s)
Fromentin R., DaFonseca S., Costiniuk C.T., El-Far M., Procopio F.A., Hecht F.M., Hoh R., Deeks S.G., Hazuda D.J., Lewin S.R., Routy J.P., Sékaly R.P., Chomont N.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
18/02/2019
Peer-reviewed
Oui
Volume
10
Number
1
Pages
814
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
HIV persists in latently infected CD4 <sup>+</sup> T cells during antiretroviral therapy (ART). Immune checkpoint molecules, including PD-1, are preferentially expressed at the surface of persistently infected cells. However, whether PD-1 plays a functional role in HIV latency and reservoir persistence remains unknown. Using CD4 <sup>+</sup> T cells from HIV-infected individuals, we show that the engagement of PD-1 inhibits viral production at the transcriptional level and abrogates T-cell receptor (TCR)-induced HIV reactivation in latently infected cells. Conversely, PD-1 blockade with the monoclonal antibody pembrolizumab enhances HIV production in combination with the latency reversing agent bryostatin without increasing T cell activation. Our results suggest that the administration of immune checkpoint blockers to HIV-infected individuals on ART may facilitate latency disruption.
Keywords
Antibodies, Monoclonal, Humanized/pharmacology, Antiretroviral Therapy, Highly Active, B7-H1 Antigen/pharmacology, Bryostatins/pharmacology, CD4-Positive T-Lymphocytes/virology, HIV-1/physiology, Humans, Lymphocyte Activation/drug effects, Programmed Cell Death 1 Receptor/antagonists & inhibitors, Programmed Cell Death 1 Receptor/metabolism, Virus Latency/drug effects
Pubmed
Web of science
Open Access
Yes
Create date
11/03/2019 18:28
Last modification date
20/08/2019 14:32
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