Modalities of interleukin-7-induced human immunodeficiency virus permissiveness in quiescent T lymphocytes.
The metabolic and cell cycle status of primary T lymphocytes conditions their susceptibility to human immunodeficiency virus (HIV) and HIV-derived vectors. While in fully quiescent T lymphocytes the reverse transcription and nuclear import of these retroelements are impaired, leading to an abortive infection, various stimuli can induce a state of virus permissiveness. Here, we studied the modalities by which interleukin-7 (IL-7), an important controller of T-cell homeostasis, exerts this effect. IL-7-exposed cord blood T lymphocytes proliferated and were efficiently transduced by HIV-derived vectors. In contrast, similarly treated adult peripheral blood (PB) T lymphocytes failed to divide, and only a subset of these cells became infectible. HIV-resistant and -sensitive subsets of IL-7-treated PB T lymphocytes differed in cell cycle status but not in naïve, memory, or activation phenotypes. Nuclear factor of activated T cells was not induced by IL-7, and cyclosporine did not prevent HIV-mediated gene transfer. Furthermore, the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin blocked IL-7-induced cell survival and Bcl-2 synthesis but had no effect on the acquisition of HIV susceptibility, suggesting that IL-7-induced HIV type 1 permissiveness is not mediated by the PI-3 K pathway and that, perhaps, the Jak/STAT5 pathway, the other known mediator of IL-7-triggered signaling in T cells, governs this process.
Department of Genetics and Microbiology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Odile
O
Ducrey-Rundquist
Mireille
M
Guyader
Didier
D
Trono
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D005434:Flow Cytometry; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D015851:Interleukin-7 / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000821:virology; D008213:Lymphocyte Activation; D016176:T-Lymphocyte Subsets / Q000502:physiology* / Q000821:virology*; D014161:Transduction, Genetic
D015851:Interleukin-7