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

• Published in: The Journal of clinical investigation Vol. 115; no. 1; pp. 128 - 137
• Main Authors: Wang, Feng-Xiang, Xu, Yan, Sullivan, Julie, Souder, Emily, Argyris, Elias G, Acheampong, Edward A, Fisher, Jaime, Sierra, Maria, Thomson, Michael M, Najera, Rafael, Frank, Ian, Kulkosky, Joseph, Pomerantz, Roger J, Nunnari, Giuseppe
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.01.2005
• Subjects: Anti-HIV Agents - therapeutic use; Antiretroviral Therapy, Highly Active; Biomedical research; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; Cells; Cells, Cultured; Cytokines; Cytotoxicity; Drug therapy; Gene Expression Regulation, Viral - drug effects; HIV Envelope Protein gp120 - genetics; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - genetics; HIV Infections - virology; HIV Long Terminal Repeat - genetics; HIV-1 - classification; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - physiology; Homeostasis; Humans; Infections; Interleukin-2 - pharmacology; Interleukin-7 - pharmacology; Lymphocyte Activation - drug effects; Lymphocytes; Phylogeny; Phytohemagglutinins - pharmacology; Plasma; Proviruses - drug effects; Proviruses - physiology; RNA, Viral - genetics; RNA, Viral - metabolism; Species Specificity; Viral infections; Virus Activation - drug effects; Virus Replication - drug effects
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci200522574

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.