
<ArticleTitle>Endothelial cells enhance human immunodeficiency virus type 1 replication in macrophages through a C/EBP-dependent mechanism.</ArticleTitle>
<AbstractText>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 <prot>C/EBPbeta</prot> is critical for macrophages to respond to endothelial cell-derived signals. We show that endothelial cells significantly enhance <prot>C/EBPbeta</prot> 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 <prot>ICAM-1</prot> and <prot>interleukin 6</prot>, 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 <prot>C/EBPbeta</prot>, provide a microenvironment that supports HIV-1 replication in monocytes/macrophages.</AbstractText>
