C/EBP proteins activate transcription from the human immunodeficiency virus type 1 long terminal repeat in macrophages/monocytes.
Three binding sites for C/EBP proteins are found in the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) (V. M. Tesmer, A. Rajadhyaksha, J. Babin, and M. Bina, Proc. Natl. Acad. Sci. USA 90:7298-7302, 1993). We have determined the functional role of C/EBP proteins and C/EBP sites in regulating transcription from the HIV-1 LTR in monocytes/macrophages. Inhibition of endogenous C/EBP proteins, using either an excess of C/EBP binding sites or a trans-dominant negative inhibitor, demonstrated that C/EBP proteins are required for basal and activated levels of HIV-1 LTR transcription in the promonocytic cell line U937. Northern (RNA) blots and binding assays showed that NF-IL6 is the only known C/EBP family member which is increased when U937 cells are activated. Mutational analyses of the HIV-1 LTR showed that one C/EBP site is required for normal LTR transcription both before and after cellular activation and that the two 3' C/EBP sites are functionally equivalent. However, transcription from crippled HIV-1 LTRs lacking C/EBP sites can still be induced following activation of U937 cells. Several models are suggested for how elevated NF-IL6 may participate in an autostimulatory loop involving HIV infection, macrophage activation, cytokine expression, and HIV replication.
Henderson
A J
AJ
Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Zou
X
X
Calame
K L
KL
D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D002454:Cell Differentiation; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015870:Gene Expression; D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008156:Luciferases / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism / Q000821:virology; D009687:Nuclear Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000096:biosynthesis; D015183:Restriction Mapping; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D022762:CCAAT-Enhancer-Binding Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D008156:Luciferases; D015500:Chloramphenicol O-Acetyltransferase