Figure 4

Important C/EBP transcription factor signaling in monocyte-macrophages: (a) Activation of HIV transcription: C/EBP, located in the cytoplasm of the cell, can become phosphorylated by the MAP kinase, PKA, or cdk9 through a variety of pathways. Once phosphorylated, C/EBP is translocated into the nucleus where it can transactivate the LTR. In addition, C/EBP associates with histone acetyl transferases such as p300, which when bound to the LTR, make the chromosome accessible for RNA polymerases to bind and transcribe the integrated proviral DNA. Finally, association of C/EBP with APOBEC3G allows for better reverse transcription in the cytoplasm. (b) Inhibition of HIV transcription: The binding of IFNβ to its receptor begins a JAK/STAT signaling cascade that results in increased production of C/EBP3 (LIP). C/EBP3, which does not contain the transactivation domain of full-length C/EBPs, does not interact with histone acetyl transferases and when bound to the LTR, blocks the binding of full-length C/EBPs, thereby leading to a repression of LTR activity.