Differences in inducibility of the latent HIV reservoir in perinatal and adult infection. Academic Article uri icon

Overview

abstract

  • The 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.

publication date

  • February 27, 2020

Research

keywords

  • CD4-Positive T-Lymphocytes
  • Disease Reservoirs
  • HIV Infections
  • HIV-1
  • Virus Latency

Identity

PubMed Central ID

  • PMC7101150

Scopus Document Identifier

  • 85081656112

Digital Object Identifier (DOI)

  • 10.1172/jci.insight.134105

PubMed ID

  • 31999647

Additional Document Info

volume

  • 5

issue

  • 4