IL-7 is a potent and proviral strain–specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART
Feng-Xiang Wang, … , Roger J. Pomerantz, Giuseppe Nunnari
Feng-Xiang Wang, … , Roger J. Pomerantz, Giuseppe Nunnari
Published January 3, 2005
Citation Information: J Clin Invest. 2005;115(1):128-137. https://doi.org/10.1172/JCI22574.
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Article AIDS/HIV

IL-7 is a potent and proviral strain–specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART

Abstract

The persistence of HIV-1 in virally suppressed infected individuals on highly active antiretroviral therapy (HAART) remains a major therapeutic problem. The use of cytokines has been envisioned as an additional therapeutic strategy to stimulate latent proviruses in these individuals. Immune activation therapy using IL-2 has shown some promise. In the present study, we found that IL-7 was significantly more effective at enhancing HIV-1 proviral reactivation than either IL-2 alone or IL-2 combined with phytohemagglutinin (PHA) in CD8-depleted PBMCs. IL-7 also showed a positive trend for inducing proviral reactivation from resting CD4+ T lymphocytes from HIV-1–infected patients on suppressive HAART. Moreover, the phylogenetic analyses of viral envelope gp120 genes from induced viruses indicated that distinct proviral quasispecies had been activated by IL-7, as compared with those activated by the PHA/IL-2 treatment. These studies thus demonstrate that different activators of proviral latency may perturb and potentially deplete only selected, specific portions of the proviral archive in virally suppressed individuals. The known immunomodulatory effects of IL-7 could be combined with its ability to stimulate HIV-1 replication from resting CD4+ T lymphocytes, in addition to other moieties, to potentially deplete HIV-1 reservoirs and lead to the rational design of immune-antiretroviral approaches.

Authors

Feng-Xiang Wang, Yan Xu, Julie Sullivan, Emily Souder, Elias G. Argyris, Edward A. Acheampong, Jaime Fisher, Maria Sierra, Michael M. Thomson, Rafael Najera, Ian Frank, Joseph Kulkosky, Roger J. Pomerantz, Giuseppe Nunnari

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Phylogenetic analyses of HIV-1 envelope gene sequences of proviral DNA a...
Phylogenetic analyses of HIV-1 envelope gene sequences of proviral DNA and cytokine-induced virion RNA from the same cell populations. The full-length of gp120 V1 to V5 regions were cloned and sequenced directly from proviral DNA of PBMCs and purified, resting CD4+ T lymphocytes, and IL-7 or PHA/IL-2–induced virion RNA for 4 patients (numbers 1–4, A–D). Proviral DNA sequences are presented by black stars (open stars for those strains from PBMC and filled for those of resting CD4+ T lymphocytes). IL-7–induced viral RNA sequences are indicated by blue squares (open squares for PBMC and IL-7–induced and filled squares for resting CD4+ T lymphocyte and IL–induced). PHA/IL-2–induced viral RNA sequences are indicated by red circles (open circles for those induced by PBMC with PHA/IL-2 and filled circles for those induced by resting CD4+ T- lymphocyte with PHA/IL-2). Growth of patient 4’s virus from PBMCs with PHA/IL-2 was from 10/04/2001. All sequences are shown with HXB2 (GenBank accession no. K03455) as the reference outgroup. Branch lengths are drawn in proportion to the number of nucleotide substitutions per site, and bootstrap probabilities (1,000 iterations) exceeding 70% for each node are noted.