Differences in inducibility of the latent HIV reservoir in perinatal and adult infection
PublisherAmerican Society for Clinical Investigation
MetadataShow full item record
AbstractThe HIV latent reservoir in resting memory CD4+ T cells precludes cure. Therapeutics to reactivate and eliminate this reservoir are in clinical trials in adults, but not yet in pediatric populations. We determined, ex vivo, the inducibility of the latent reservoir in perinatal infection as compared with adult infections using the Tat/rev induced limiting dilution assay (TILDA), in which a single round (12 hours) of CD4+ T cell stimulation with PMA/ionomycin maximally activates T cells and leads to proviral expression with multiply spliced HIV RNA production. Markers of immune activation and exhaustion were measured to assess interactions with inducibility. Although rates of T cell activation with PMA/ionomycin were similar, the latent reservoir in perinatal infection was slower to reactivate and of lower magnitude compared with adult infection, independent of proviral load. An enhanced TILDA with the addition of phytohemagglutin and a duration of 18 hours augmented proviral expression in perinatal but not adult infection. The baseline HLA-DR+CD4+ T cell level was significantly lower in perinatal compared with adult infections, but not correlated with induced reservoir size. These data support the hypothesis that there are differences in kinetics of latency reversal and baseline immune activation in perinatal compared with adult infections, with implications for latency reversal strategies toward reservoir clearance and remission.
SponsorsThis research was supported by the NIH (R01 HD080474 [to DP], PO1 AI131365 [to DP], U01 1U01AI135941, [to DP]), the BELIEVE Collaboratory (1UM1AI26617), EPIICAL (16108367), International Maternal Pediatric Adolescent Clinical Trials Laboratory Center (UM1AI106716), and the Johns Hopkins Center for AIDS Research (P30 AI094189).
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85081656112&doi=10.1172%2fjci.insight.134105&partnerID=40&md5=74cb70ec6d5915311b43cc41383324ab; http://hdl.handle.net/10713/12377
- Inter-Laboratory Reproducibility of Inducible HIV-1 Reservoir Quantification by TILDA.
- Authors: Lungu C, Procopio FA, Overmars RJ, Beerkens RJJ, Voermans JJC, Rao S, Prins HAB, Rokx C, Pantaleo G, Vijver DAMCV, Mahmoudi T, Boucher CAB, Gruters RA, Kampen JJAV
- Issue date: 2020 Sep 2
- HIV DNA subspecies persist in both activated and resting memory CD4+ T cells during antiretroviral therapy.
- Authors: Murray JM, Zaunders JJ, McBride KL, Xu Y, Bailey M, Suzuki K, Cooper DA, Emery S, Kelleher AD, Koelsch KK, PINT Study Team.
- Issue date: 2014 Mar
- Analysis of human immunodeficiency virus type 1 gene expression in latently infected resting CD4+ T lymphocytes in vivo.
- Authors: Hermankova M, Siliciano JD, Zhou Y, Monie D, Chadwick K, Margolick JB, Quinn TC, Siliciano RF
- Issue date: 2003 Jul
- HIV-Specific Granzyme B-Secreting but Not Gamma Interferon-Secreting T Cells Are Associated with Reduced Viral Reservoirs in Early HIV Infection.
- Authors: Yue FY, Cohen JC, Ho M, Rahman AKMN, Liu J, Mujib S, Saiyed A, Hundal S, Khozin A, Bonner P, Liu D, Benko E, Kovacs C, Ostrowski M
- Issue date: 2017 Apr 15
- Establishment and Reversal of HIV-1 Latency in Naive and Central Memory CD4+ T Cells In Vitro.
- Authors: Zerbato JM, Serrao E, Lenzi G, Kim B, Ambrose Z, Watkins SC, Engelman AN, Sluis-Cremer N
- Issue date: 2016 Sep 15