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-β induced the 16-kD inhibitory C/EBPβ isoform and coincidentally repressed HIV-1 LTR transcription. C/EBPβ 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/EBPβ, but pulmonary tuberculosis abolished inhibitory C/EBPβ 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/EBPβ 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.
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5 October 1998
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October 05 1998
Type I Interferon Induces Inhibitory 16-kD CCAAT/ Enhancer Binding Protein (C/EBP)β, Repressing the HIV-1 Long Terminal Repeat in Macrophages: Pulmonary Tuberculosis Alters C/EBP Expression, Enhancing HIV-1 Replication
Yoshihiro Honda,
Yoshihiro Honda
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
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Linda Rogers,
Linda Rogers
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
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Koh Nakata,
Koh Nakata
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
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Ben-Yang Zhao,
Ben-Yang Zhao
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
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Richard Pine,
Richard Pine
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
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Yushi Nakai,
Yushi Nakai
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
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Katsushi Kurosu,
Katsushi Kurosu
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
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William N. Rom,
William N. Rom
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
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Michael Weiden
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
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Yoshihiro Honda,
Linda Rogers,
Koh Nakata,
Ben-Yang Zhao,
Richard Pine,
Yushi Nakai,
Katsushi Kurosu,
William N. Rom,
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
Address correspondence to Michael Weiden, Division of Pulmonary and Critical Care Medicine and Bellevue Chest Service, NYU Medical Center, 550 First Ave., New York, NY 10016. Phone: 212-263-7889; Fax: 212-263-8501; E-mail: [email protected]
Y. Honda's current address is Department of Medicine, Sendai Kosei Hospital, Sendai 980, Japan.
Received:
May 22 1998
Revision Received:
July 06 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 188 (7): 1255–1265.
Article history
Received:
May 22 1998
Revision Received:
July 06 1998
Citation
Yoshihiro Honda, Linda Rogers, Koh Nakata, Ben-Yang Zhao, Richard Pine, Yushi Nakai, Katsushi Kurosu, William N. Rom, Michael Weiden; Type I Interferon Induces Inhibitory 16-kD CCAAT/ Enhancer Binding Protein (C/EBP)β, Repressing the HIV-1 Long Terminal Repeat in Macrophages: Pulmonary Tuberculosis Alters C/EBP Expression, Enhancing HIV-1 Replication . J Exp Med 5 October 1998; 188 (7): 1255–1265. doi: https://doi.org/10.1084/jem.188.7.1255
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