PD-1 blockade potentiates HIV latency reversal ex vivo in CD4+ T cells from ART-suppressed individuals.
Rémi FromentinSandrina DaFonsecaCecilia T CostiniukMohamed El-FarFrancesco Andrea ProcopioFrederick M HechtRebecca HohSteven G DeeksDaria J HazudaSharon R LewinJean-Pierre RoutyRafick-Pierre SékalyNicolas ChomontPublished in: Nature communications (2019)
HIV persists in latently infected CD4+ 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+ 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.
Keyphrases
- antiretroviral therapy
- hiv infected
- hiv positive
- human immunodeficiency virus
- hiv infected patients
- hiv aids
- induced apoptosis
- monoclonal antibody
- hiv testing
- cell cycle arrest
- oxidative stress
- advanced non small cell lung cancer
- south africa
- hepatitis c virus
- endoplasmic reticulum stress
- angiotensin ii
- high glucose
- men who have sex with men