CCAAT/Enhancer Binding Protein (C/EBP) Sites are Required for HIV-1 Replication in Primary Macrophages but not CD4+T Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 94; no. 16; pp. 8714 - 8719
• Main Authors: Henderson, A. J., Calame, K. L.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 05.08.1997; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences of the USA
• Subjects: Binding sites; Binding Sites - immunology; Biochemistry; Biological Sciences; CCAAT-Enhancer-Binding Proteins; CD4 Antigens; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; Cell lines; Cultured cells; DNA; DNA-Binding Proteins - physiology; HIV; HIV 1; HIV-1 - physiology; Human immunodeficiency virus; Humans; Immunity (Disease); Infections; Jurkat Cells; Macrophages; Macrophages - immunology; Macrophages - virology; Nuclear Proteins - physiology; Organ Specificity; Polymerase chain reaction; Proteins; T lymphocytes; Virus Replication; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.16.8714

The importance of CCAAT/enhancer binding proteins (C/EBPs) and binding sites for HIV-1 replication in primary macrophages, T cell lines and primary CD4+T cells was examined. When lines overexpressing the C/EBP dominant-negative protein LIP were infected with HIV-1, replication occurred in Jurkat T cells but not in U937 promonocytes, demonstrating a requirement for C/EBP activators by HIV-1 only in promonocytes. Primary macrophages did not support the replication of HIV-1 harboring mutant C/EBP binding sites in the long terminal repeat but Jurkat, H9 and primary CD4+T cells supported replication of wild-type and mutant HIV-1 equally well. Thus the requirement for C/EBP sites is also confined to monocyte/macrophages. The requirement for C/EBP proteins and sites identifies the first uniquely macrophage-specific regulatory mechanism for HIV-1 replication.