High-level replication of human immunodeficiency virus in thymocytes requires NF-kappa B activation through interaction with thymic epithelial cells

Citation
L. Chene et al., High-level replication of human immunodeficiency virus in thymocytes requires NF-kappa B activation through interaction with thymic epithelial cells, J VIROLOGY, 73(3), 1999, pp. 2064-2073
Citations number
69
Categorie Soggetti
Microbiology
Journal title
JOURNAL OF VIROLOGY
ISSN journal
0022538X → ACNP
Volume
73
Issue
3
Year of publication
1999
Pages
2064 - 2073
Database
ISI
SICI code
0022-538X(199903)73:3<2064:HROHIV>2.0.ZU;2-R
Abstract
We have previously demonstrated that interaction of infected thymocytes wit h autologous thymic epithelial cells (TEC) is a prerequisite for a high lev el of human immunodeficiency virus type 1 (HIV-1) replication in thymocytes (M. Rothe, L. Chene, M, Nugeyre, F. Barre-Sinoussi, and N. Israel, J. Viro l. 72:5852-5861, 1998). We report here that this activation of HIV replicat ion takes place at the transcriptional level through activation of the Rel/ NF-kappa B transcription factors. We first demonstrate that an HIV-1 provir us (SF-2 strain) very effectively replicates in thymocytes cocultured with TEC whereas this provirus, with kappa B sites deleted, fails to replicate. We provide evidence that several NF-kappa B complexes are constitutively fo und in the nuclei of thymocytes either freshly isolated from the thymus or maintained in coculture with autologous or heterologous TEC, The prevalent complex: is the heterodimer p50-p65, NF-kappa B activity is tightly correla ted with the transcriptional activity of a long terminal repeat (LTR) of HI V-1 transfected in thymocytes. The cotransfection of this LTR with a mutate d I kappa B alpha molecule formally demonstrates that LTR transactivation i s regulated by members of the Rel/NF-kappa B family in thymocytes. We also showed that tumor necrosis factor (TNF) and to a lesser extent interleukin- 1 (IL-1), secreted within the coculture, induce NF-kappa B activity and a c orrelative LTR transactivation. However IL-7, a crucial factor for thymopoi esis that is secreted mainly by TEC, is a necessary cofactor for NF-kappa B activation elicited by TNF or IL-1, Together, these data indicate that NF- kappa B activation, required for a high level of HIV replication in thymocy tes, is regulated in a specific manner in the thymic microenvironment which provides the necessary cytokines: TNF, IL-1, and IL-7.