부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.virol.2006.02.019 Byline: Elizabeth Z. Managlia, Alan Landay, Lena Al-Harthi Keywords: IL-7; HIV; NFAT Abstract: Interleukin (IL)-7 plays several roles critical to T cell maturation, survival, and homeostasis. Because of these functions, IL-7 is under investigation as an immune-modulator for therapeutic use in lymphopenic clinical conditions, including HIV. We reported that naive T cells, typically not permissive to HIV, can be productively infected when pre-treated with IL-7. We evaluated the mechanism by which IL-7-mediates this effect. IL-7 potently up-regulated the transcriptional factor NFAT, but had no effect on NF[kappa]B. Blocking NFAT activity using a number of reagents, such as Cyclosporin A, FK-506, or the NFAT-specific inhibitor known as VIVIT peptide, all markedly reduced IL-7-mediated induction of HIV replication in naive T cells. Additional neutralization of cytokines present in IL-7-treated cultures and/or those that have NFAT-binding sequences within their promotors indicated that IL-10, IL-4, and most significantly IFN[gamma], all contribute to IL-7-induction of HIV productive replication in naive T cells. These data clarify the mechanism by which IL-7 can overcome the block to HIV productive infection in naive T cells, despite their quiescent cell status. These findings are relevant to the treatment of HIV disease and understanding HIV pathogenesis in the naive CD4+ T cell compartment, especially in light of the vigorous pursuit of IL-7 as an in vivo immune modulator. Author Affiliation: Department of Immunology/Microbiology, Rush University Medical Center, 1735 West Harrison Street, 614 Cohn, Chicago, IL 60612, USA Article History: Received 4 January 2006; Revised 8 February 2006; Accepted 13 February 2006