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PMID: 9763605 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Type I interferon induces inhibitory 16-kD CCAAT/ enhancer binding protein (C/EBP)beta, repressing the HIV-1 long terminal repeat in macrophages: pulmonary tuberculosis alters C/EBP expression, enhancing HIV-1 replication.

The Journal of experimental medicine ·Vol. 188 ·No. 7 ·1998-10-05 ·Pages 1255-65

Honda Y, Rogers L, Nakata K, Zhao BY, Pine R, Nakai Y, Kurosu K, Rom WN, Weiden M

Abstract

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-beta induced the 16-kD inhibitory C/EBPbeta isoform and coincidentally repressed HIV-1 LTR transcription. C/EBPbeta 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/EBPbeta, but pulmonary tuberculosis abolished inhibitory C/EBPbeta 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/EBPbeta 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.

MeSH Terms
Base Sequence Binding Sites Bronchoalveolar Lavage CCAAT-Enhancer-Binding Proteins DNA, Viral DNA-Binding Proteins/metabolism Down-Regulation HIV Long Terminal Repeat HIV-1/physiology Humans Interferon-alpha/metabolism,pharmacology Interferon-beta/pharmacology Macrophages/drug effects,metabolism Macrophages, Alveolar/metabolism Molecular Sequence Data Mycobacterium tuberculosis/physiology Nuclear Proteins/metabolism Promoter Regions, Genetic Transcription Factors Tuberculosis, Pulmonary/metabolism Virus Replication
Chemicals
CCAAT-Enhancer-Binding Proteins DNA, Viral DNA-Binding Proteins Interferon-alpha Nuclear Proteins Transcription Factors Interferon-beta
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Honda Y
Division of Pulmonary and Critical Care Medicine and Bellevue Chest Service, New York University Medical Center, New York 10016, USA.
Rogers L
Nakata K
Zhao B Y
Pine R
Nakai Y
Kurosu K
Rom W N
Weiden M
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.188.7.1255
Published
1998-10-05
Pages
1255-65
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2212491
Subset
IM
Grants
NCRR NIH HHS · MO1 RR00096 · United States
NHLBI NIH HHS · HL-51470 · United States
NHLBI NIH HHS · HL-51494 · United States
External Links
PubMed source DOI: 10.1084/jem.188.7.1255 PMC Full Text View journal details
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