Journal article
Programmed cell death-1 contributes to the establishment and maintenance of HIV-1 latency
VA Evans, RM Van Der Sluis, A Solomon, A Dantanarayana, C McNeil, R Garsia, S Palmer, R Fromentin, N Chomont, RP Sékaly, PU Cameron, SR Lewin
AIDS | LIPPINCOTT WILLIAMS & WILKINS | Published : 2018
Abstract
Objective: In HIV-infected individuals on antiretroviral therapy (ART), latent HIV is enriched in CD4 + T cells expressing immune checkpoint molecules, in particular programmed cell death-1 (PD-1). We therefore assessed the effect of blocking PD-1 on latency, both in vitro and in vivo. Methods: HIV latency was established in vitro following coculture of resting CD4 + T cells with myeloid dendritic cells. Expression of PD-1 was quantified by flow cytometry, and latency assessed in sorted PD-1 high and PD-1 low/-nonproliferating CD4 + memory T cells. The role of PD-1 in the establishment of latency was determined by adding anti-PD-1 (pembrolizumab) to cocultures before and after infection. In ..
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Awarded by National Institute of Allergy and Infectious Diseases
Funding Acknowledgements
Anti-PD-1 antibodies were kindly supplied by Merck (MK-3475/pembrolizumab; in-vitro studies) and Bristol Myers Squibb (nivolumab; supplied under their Special Access Scheme for the in-vivo study). This work was supported by funds from the American Foundation for AIDS Research, amfAR (grant numbers 108237-51-RGRL and 109226-58-RGRL); the National Health and Medical Research Council (NHMRC) of Australia (grant number APP1041795); and the National Institutes of Health Delaney AIDS Research Enterprise (DARE) to find a cure collaboratory (grant numbers U19 AI096109 and UM1AI126611). S.R.L. is an NHMRC Practitioner Fellow. The authors have no conflicting financial interests.