CCAAT/Enhancer Binding Proteins Are Not Required for HIV-1 Entry but Regulate Proviral Transcription by Recruiting Coactivators to the Long-Terminal Repeat in Monocytic Cells

摘要

CCAAT/enhancer binding proteins (C/EBP) have been shown to be required for HIV-1 transcription and replication in macrophages. However, whether these transcription factors influence the ability of virus to establish infection by altering cytokine or receptor expression or primarily regulate HIV-1 transcription has not been determined. By inhibiting endogenous C/EBP activity with a dominant-negative protein, we demonstrate that functional C/EBPs are not required for HIV-1 infection and that these factors influence replication by a transcriptional mechanism. C/EBPβ recruits coactivators to the HIV-1 long-terminal repeat (LTR) and physically interacts with histone acetyltransferase (HAT) complexes, suggesting that C/EBPs participate in remodeling the chromatin organization of the HIV-1 provirus. Furthermore, overexpression of a C/EBP dominant-negative inhibits displacement of nucleosomes located at the HIV-1 transcriptional start site. These results provide insight into the general mechanisms by which C/EBPs regulate macrophage-restricted HIV-1 transcription.