TY - JOUR
T1 - PD-1 blockade potentiates HIV latency reversal ex vivo in CD4 + T cells from ART-suppressed individuals
AU - Fromentin, Rémi
AU - DaFonseca, Sandrina
AU - Costiniuk, Cecilia T.
AU - El-Far, Mohamed
AU - Procopio, Francesco Andrea
AU - Hecht, Frederick M.
AU - Hoh, Rebecca
AU - Deeks, Steven G.
AU - Hazuda, Daria J.
AU - Lewin, Sharon R.
AU - Routy, Jean Pierre
AU - Sékaly, Rafick Pierre
AU - Chomont, Nicolas
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85061693955&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-08798-7
DO - 10.1038/s41467-019-08798-7
M3 - Article
C2 - 30778080
AN - SCOPUS:85061693955
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 814
ER -