J. Exp. Med., Volume 188, Number 7, October 5, 1998 1255-1265

Type I Interferon Induces Inhibitory 16-kD CCAAT/ Enhancer Binding Protein (C/EBP), Repressing the HIV-1 Long Terminal Repeat in Macrophages: Pulmonary Tuberculosis Alters C/EBP Expression, Enhancing HIV-1 Replication

By Yoshihiro Honda,^* Linda Rogers,^* Koh Nakata, Ben-Yang Zhao, Richard Pine, Yushi Nakai,^§ Katsushi Kurosu,^* William N. Rom,^* and Michael Weiden^*

From the ^* Division of Pulmonary and Critical Care Medicine and Bellevue Chest Service, New York University Medical Center, New York 10016; the  Department of Microbiology and Infection, Institute of Medical Science, Tokyo University, Tokyo 108, Japan; the ^§ Department of Medicine, Sendai Kosei Hospital, Sendai 980, Japan; and the  Public Health Research Institute, New York 10016

We have previously observed that HIV-1 replication is suppressed in uninflamed lung and increased during tuberculosis. In vitro THP-1 cell-derived macrophages inhibited HIV-1 replication after infection with Mycobacterium tuberculosis. Suppression of HIV-1 replication was associated with inhibition of the HIV-1 long terminal repeat (LTR) and induction of ISGF-3, a type I interferon (IFN)-specific transcription factor. Repression of the HIV-1 LTR required intact CCAAT/enhancer binding protein (C/EBP) sites. THP-1 cell-derived macrophages infected with M. tuberculosis, lipopolysaccharide, or IFN- induced the 16-kD inhibitory C/EBP isoform and coincidentally repressed HIV-1 LTR transcription. C/EBP was the predominant C/EBP family member produced in THP-1 macrophages during HIV-1 LTR repression. In vivo, alveolar macrophages from uninflamed lung strongly expressed inhibitory 16-kD C/EBP, but pulmonary tuberculosis abolished inhibitory C/EBP expression and induced a novel C/EBP DNA binding protein. Therefore, in vitro, proinflammatory stimulation produces an IFN response inhibiting viral replication by induction of a C/EBP transcriptional repressor. THP-1 cell-derived macrophages stimulated with type I IFN are similar to alveolar macrophages in the uninflamed lung in vivo. In contrast, the cellular immune response in active pulmonary tuberculosis disrupts this innate immunity, switching C/EBP expression and allowing high level viral replication.

interferon ;  CCAAT/enhancer binding protein ;  HIV-1 long terminal repeat;  tuberculosis;  repression

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Komuro, I., Sunazuka, T., Akagawa, K. S., Yokota, Y., Iwamoto, A., Omura, S. (2008). Erythromycin derivatives inhibit HIV-1 replication in macrophages through modulation of MAPK activity to induce small isoforms of C/EBP{beta}. Proc. Natl. Acad. Sci. USA 105: 12509-12514 [Abstract] [Full Text]  
• Mohan, M., Aye, P. P., Borda, J. T., Alvarez, X., Lackner, A. A. (2008). CCAAT/Enhancer Binding Protein {beta} Is a Major Mediator of Inflammation and Viral Replication in the Gastrointestinal Tract of Simian Immunodeficiency Virus-Infected Rhesus Macaques. Am. J. Pathol. 173: 106-118 [Abstract] [Full Text]  
• Dudaronek, J. M., Barber, S. A., Clements, J. E. (2007). CUGBP1 Is Required for IFNbeta-Mediated Induction of Dominant-Negative CEBPbeta and Suppression of SIV Replication in Macrophages. J. Immunol. 179: 7262-7269 [Abstract] [Full Text]  
• Wahl, S. M., Greenwell-Wild, T., Vazquez, N. (2006). HIV accomplices and adversaries in macrophage infection. J. Leukoc. Biol. 80: 973-983 [Abstract] [Full Text]  
• Cassol, E., Alfano, M., Biswas, P., Poli, G. (2006). Monocyte-derived macrophages and myeloid cell lines as targets of HIV-1 replication and persistence. J. Leukoc. Biol. 80: 1018-1030 [Abstract] [Full Text]  
• Tanaka, N., Hoshino, Y., Gold, J., Hoshino, S., Martiniuk, F., Kurata, T., Pine, R., Levy, D., Rom, W. N., Weiden, M. (2005). Interleukin-10 Induces Inhibitory C/EBP{beta} through STAT-3 and Represses HIV-1 Transcription in Macrophages. Am. J. Respir. Cell Mol. Bio. 33: 406-411 [Abstract] [Full Text]  
• Espert, L., Degols, G., Lin, Y.-L., Vincent, T., Benkirane, M., Mechti, N. (2005). Interferon-induced exonuclease ISG20 exhibits an antiviral activity against human immunodeficiency virus type 1. J. Gen. Virol. 86: 2221-2229 [Abstract] [Full Text]  
• Prabhakar, S., Qiao, Y., Canova, A., Tse, D. B., Pine, R. (2005). IFN-{alpha}{beta} Secreted during Infection Is Necessary but Not Sufficient for Negative Feedback Regulation of IFN-{alpha}{beta} Signaling by Mycobacterium tuberculosis. J. Immunol. 174: 1003-1012 [Abstract] [Full Text]  
• Emori, Y., Ikeda, T., Ohashi, T., Masuda, T., Kurimoto, T., Takei, M., Kannagi, M. (2004). Inhibition of human immunodeficiency virus type 1 replication by Z-100, an immunomodulator extracted from human-type tubercle bacilli, in macrophages. J. Gen. Virol. 85: 2603-2613 [Abstract] [Full Text]  
• Hoshino, Y., Tse, D. B., Rochford, G., Prabhakar, S., Hoshino, S., Chitkara, N., Kuwabara, K., Ching, E., Raju, B., Gold, J. A., Borkowsky, W., Rom, W. N., Pine, R., Weiden, M. (2004). Mycobacterium tuberculosis-Induced CXCR4 and Chemokine Expression Leads to Preferential X4 HIV-1 Replication in Human Macrophages. J. Immunol. 172: 6251-6258 [Abstract] [Full Text]  
• Raju, B., Hoshino, Y., Kuwabara, K., Belitskaya, I., Prabhakar, S., Canova, A., Gold, J. A., Condos, R., Pine, R. I., Brown, S., Rom, W. N., Weiden, M. D. (2004). Aerosolized Gamma Interferon (IFN-{gamma}) Induces Expression of the Genes Encoding the IFN-{gamma}-Inducible 10-Kilodalton Protein but Not Inducible Nitric Oxide Synthase in the Lung during Tuberculosis. Infect. Immun. 72: 1275-1283 [Abstract] [Full Text]  
• Gold, J. A., Hoshino, Y., Tanaka, N., Rom, W. N., Raju, B., Condos, R., Weiden, M. D. (2004). Surfactant Protein A Modulates the Inflammatory Response in Macrophages during Tuberculosis. Infect. Immun. 72: 645-650 [Abstract] [Full Text]  
• Komuro, I., Yokota, Y., Yasuda, S., Iwamoto, A., Kagawa, K. S. (2003). CSF-induced and HIV-1-mediated Distinct Regulation of Hck and C/EBP{beta} Represent a Heterogeneous Susceptibility of Monocyte-derived Macrophages to M-tropic HIV-1 Infection. J. Exp. Med. 198: 443-453 [Abstract] [Full Text]  
• Condos, R., Raju, B., Canova, A., Zhao, B.-Y., Weiden, M., Rom, W. N., Pine, R. (2003). Recombinant Gamma Interferon Stimulates Signal Transduction and Gene Expression in Alveolar Macrophages In Vitro and in Tuberculosis Patients. Infect. Immun. 71: 2058-2064 [Abstract] [Full Text]  
• Perez-Bercoff, D., David, A., Sudry, H., Barre-Sinoussi, F., Pancino, G. (2003). Fc{gamma} Receptor-Mediated Suppression of Human Immunodeficiency Virus Type 1 Replication in Primary Human Macrophages. J. Virol. 77: 4081-4094 [Abstract] [Full Text]  
• Rice, J., Connor, R., Worgall, S., Moore, J. P., Leopold, P. L., Kaner, R. J., Crystal, R. G. (2002). Inhibition of HIV-1 Replication in Alveolar Macrophages by Adenovirus Gene Transfer Vectors. Am. J. Respir. Cell Mol. Bio. 27: 214-219 [Abstract] [Full Text]  
• Verani, A., Sironi, F., Siccardi, A. G., Lusso, P., Vercelli, D. (2002). Inhibition of CXCR4-Tropic HIV-1 Infection by Lipopolysaccharide: Evidence of Different Mechanisms in Macrophages and T Lymphocytes. J. Immunol. 168: 6388-6395 [Abstract] [Full Text]  
• Roy, S. K., Hu, J., Meng, Q., Xia, Y., Shapiro, P. S., Reddy, S. P. M., Platanias, L. C., Lindner, D. J., Johnson, P. F., Pritchard, C., Pages, G., Pouyssegur, J., Kalvakolanu, D. V. (2002). MEKK1 plays a critical role in activating the transcription factor C/EBP-beta -dependent gene expression in response to IFN-gamma. Proc. Natl. Acad. Sci. USA 99: 7945-7950 [Abstract] [Full Text]  
• Bouchonnet, F., Boechat, N., Bonay, M., Hance, A. J. (2002). Alpha/Beta Interferon Impairs the Ability of Human Macrophages To Control Growth of Mycobacterium bovis BCG. Infect. Immun. 70: 3020-3025 [Abstract] [Full Text]  
• Hoshino, Y., Nakata, K., Hoshino, S., Honda, Y., Tse, D. B., Shioda, T., Rom, W. N., Weiden, M. (2002). Maximal HIV-1 Replication in Alveolar Macrophages during Tuberculosis Requires both Lymphocyte Contact and Cytokines. J. Exp. Med. 195: 495-505 [Abstract] [Full Text]  
• Chang, T. L.-Y., Mosoian, A., Pine, R., Klotman, M. E., Moore, J. P. (2002). A Soluble Factor(s) Secreted from CD8+ T Lymphocytes Inhibits Human Immunodeficiency Virus Type 1 Replication through STAT1 Activation. J. Virol. 76: 569-581 [Abstract] [Full Text]  
• Lee, E. S., Zhou, H., Henderson, A. J. (2001). Endothelial Cells Enhance Human Immunodeficiency Virus Type 1 Replication in Macrophages through a C/EBP-Dependent Mechanism. J. Virol. 75: 9703-9712 [Abstract] [Full Text]  
• Lawn, S. D., Butera, S. T., Folks, T. M. (2001). Contribution of Immune Activation to the Pathogenesis and Transmission of Human Immunodeficiency Virus Type 1 Infection. Clin. Microbiol. Rev. 14: 753-777 [Abstract] [Full Text]  
• Rosati, M., Valentin, A., Patenaude, D. J., Pavlakis, G. N. (2001). CCAAT-Enhancer-Binding Protein {beta} (C/EBP{beta}) Activates CCR5 Promoter: Increased C/EBP{beta} and CCR5 in T Lymphocytes from HIV-1-Infected Individuals. J. Immunol. 167: 1654-1662 [Abstract] [Full Text]  
• Bakri, Y., Schiffer, C., Zennou, V., Charneau, P., Kahn, E., Benjouad, A., Gluckman, J. C., Canque, B. (2001). The Maturation of Dendritic Cells Results in Postintegration Inhibition of HIV-1 Replication. J. Immunol. 166: 3780-3788 [Abstract] [Full Text]  
• Darcissac, E. C. A., Truong, M.-J., Dewulf, J., Mouton, Y., Capron, A., Bahr, G. M. (2000). The Synthetic Immunomodulator Murabutide Controls Human Immunodeficiency Virus Type 1 Replication at Multiple Levels in Macrophages and Dendritic Cells. J. Virol. 74: 7794-7802 [Abstract] [Full Text]  
• Weiden, M., Tanaka, N., Qiao, Y., Zhao, B. Y., Honda, Y., Nakata, K., Canova, A., Levy, D. E., Rom, W. N., Pine, R. (2000). Differentiation of Monocytes to Macrophages Switches the Mycobacterium tuberculosis Effect on HIV-1 Replication from Stimulation to Inhibition: Modulation of Interferon Response and CCAAT/Enhancer Binding Protein {beta} Expression. J. Immunol. 165: 2028-2039 [Abstract] [Full Text]  
• Pereira, L. A., Bentley, K., Peeters, A., Churchill, M. J, Deacon, N. J. (2000). SURVEY AND SUMMARY A compilation of cellular transcription factor interactions with the HIV-1 LTR promoter. Nucleic Acids Res 28: 663-668 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS