title: 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.affiliation: Center for Human Virology and Biodefense, Division of Infectious Diseases and Environmental Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Feng-Xiang
authors.initials: FX
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Julie
authors.initials: J
authors.lastname: Sullivan
authors.forename: Emily
authors.initials: E
authors.lastname: Souder
authors.forename: Elias G
authors.initials: EG
authors.lastname: Argyris
authors.forename: Edward A
authors.initials: EA
authors.lastname: Acheampong
authors.forename: Jaime
authors.initials: J
authors.lastname: Fisher
authors.forename: Maria
authors.initials: M
authors.lastname: Sierra
authors.forename: Michael M
authors.initials: MM
authors.lastname: Thomson
authors.forename: Rafael
authors.initials: R
authors.lastname: Najera
authors.forename: Ian
authors.initials: I
authors.lastname: Frank
authors.forename: Joseph
authors.initials: J
authors.lastname: Kulkosky
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Pomerantz
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nunnari
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000821:virology*; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000145:classification* / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D010802:Phylogeny; D010835:Phytohemagglutinins / Q000494:pharmacology; D011533:Proviruses / Q000187:drug effects / Q000502:physiology; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D014775:Virus Activation / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; D007376:Interleukin-2; D015851:Interleukin-7; D010835:Phytohemagglutinins; D012367:RNA, Viral