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 activators are necessary for HIV-1 LTR activity in monocytes/macrophages. We have investigated the role that C/EBP proteins play in induction and replication of HIV-1. Ectopic expression of the dominant negative C/EBP protein LIP inhibited HIV-1 mRNA and virus production in activated U1 cells, demonstrating that C/EBP proteins are required for provirus 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 virus transcription. HIV-1 harboring mutations within two C/EBP sites were crippled in their ability to replicate in U937 promonocytic cells, indicating that these sites are required for replication. These data identify C/EBP proteins as regulators of HIV-1 expression in monocytes/macrophages.
Henderson
A J
AJ
Department of Microbiology, Columbia University College of Physicians and Surgeons, New York 10032, USA.
Connor
R I
RI
Calame
K L
KL
D000998:Antiviral Agents / Q000494:pharmacology; D001483:Base Sequence; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000821:virology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000821:virology*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D011533:Proviruses / Q000254:growth & development*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000494:pharmacology; D014158:Transcription, Genetic / Q000276:immunology; D014407:Tumor Cells, Cultured; D014771:Virion / Q000187:drug effects; D014775:Virus Activation / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology*
D000998:Antiviral Agents; D022762:CCAAT-Enhancer-Binding Proteins; C497252:CEBPD protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta