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Journal of Virology, September 2002, p. 9103-9111, Vol. 76, No. 18
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.18.9103-9111.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Modalities of Interleukin-7-Induced Human Immunodeficiency Virus Permissiveness in Quiescent T Lymphocytes

Odile Ducrey-Rundquist, Mireille Guyader, and Didier Trono*

Department of Genetics and Microbiology, Faculty of Medicine, University of Geneva, Geneva, Switzerland

Received 22 March 2002/ Accepted 7 June 2002

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.

* Corresponding author. Mailing address: CMU, 1 rue Michel-Servet, CH-1211 Geneva, Switzerland. Phone: (41 22) 702 5720. Fax: (41 22) 702 5721. E-mail: Didier.trono{at}medecine.unige.ch.

Journal of Virology, September 2002, p. 9103-9111, Vol. 76, No. 18
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.18.9103-9111.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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