Open AccessEndothelial Cells Enhance Human Immunodeficiency Virus Type 1 Replication in Macrophages through a C/EBP-Dependent Mechanism
Author(s) -
Eileen S. Lee,
Huiyu Zhou,
Andrew J. Henderson
Publication year - 2001
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.75.20.9703-9712.2001
Subject(s) - biology , microbiology and biotechnology , endothelial stem cell , viral replication , transcription factor , activator (genetics) , cell , endothelium , cell culture , ccaat enhancer binding proteins , macrophage , virology , virus , receptor , dna binding protein , in vitro , gene , biochemistry , genetics
Macrophages are early targets of human immunodeficiency virus type 1 (HIV-1) infection and serve as potential reservoirs for long-term infection. Through inflammatory mediators and direct cell contact, infected macrophages interact with neighboring cell populations, such as the endothelium, which create a microenvironment favorable for HIV-1 replication. We hypothesize that the transcriptional activator C/EBPbeta is critical for macrophages to respond to endothelial cell-derived signals. We show that endothelial cells significantly enhance C/EBPbeta binding activity and HIV-1 replication in macrophages. This increase in HIV-1 transcription is due to cell-cell contact as well as the production of soluble factors, mediated in part by ICAM-1 and interleukin 6, respectively. Furthermore, C/EBP factors are necessary for endothelial cell-dependent activation of HIV-1 transcription in macrophages, and HIV-1 induction can be inhibited by a C/EBP dominant-negative protein. In addition, C/EBP binding sites are necessary for efficient LTR activity and HIV-1 replication in the presence of endothelial cells. Taken together, these results indicate that endothelial cells, through the activation of C/EBPbeta, provide a microenvironment that supports HIV-1 replication in monocytes/macrophages.