C EBP ACTIVATORS ARE REQUIRED FOR HIV-1 REPLICATION AND PROVIRAL INDUCTION IN MONOCYTIC CELL-LINES/

Previous work has shown that C/EBP sites and C/EBP transcriptional act ivators are necessary for HIV-1 LTR activity in monocytes/macrophages. We have investigated the role that C/EBP proteins play in induction a nd replication of HIV-1. Ectopic expression of the dominant negative C /EBP protein LIP inhibited HIV-1 mRNA and virus production in activate d U1 cells, demonstrating that C/EBP proteins are required for proviru s induction. U1 lines overexpressing C/EBP activator NF-IL-6 produced more viral mRNA and virus particles following cellular activation than control lines, demonstrating that C/EBP proteins are limiting for vir us transcription. HIV-1 harboring mutations within two C/EBP sites wer e crippled in their ability to replicate in U937 promonocytic cells, i ndicating that these sites are required for replication. These data id entify C/EBP proteins as regulators of HIV-1 expression in monocytes/m acrophages.