C/EBP proteins activate transcription from the human immunodeficiency virus type 1 long terminal repeat in macrophages/monocytes

Nakata

The Journal of Experimental Medicine

et al. 2002

116

HIV-1 replication is markedly upregulated in alveolar macrophages (AM) during pulmonary tuberculosis (TB). This is associated with loss of an inhibitory CCAAT enhancer binding protein β (C/EBPβ) transcription factor and activation of nuclear factor (NF)-κB. Since the cellular immune response in pulmonary TB requires lymphocyte–macrophage interaction, a model system was developed in which lymphocytes were added to AM. Contact between lymphocytes and AM reduced inhibitory C/EBPβ, activated NF-κB, and enhanced HIV-1 replication. If contact between lymphocytes and macrophages was prevented, inhibitory C/EBPβ expression was maintained and the HIV-1 long terminal repeat (LTR) was not maximally stimulated although NF-κB was activated. Antibodies that cross-linked macrophage expressed B-7, and vascular cell adhesion molecule and CD40 were used to mimic lymphocyte contact. All three cross-linking antibodies were required to abolish inhibitory C/EBPβ expression. However, the HIV-1 LTR was not maximally stimulated and NF-κB was not activated. Maximal HIV-1–LTR stimulation required both lymphocyte-derived soluble factors, and cross-linking of macrophage expressed costimulatory molecules. High level HIV-1–LTR stimulation was also achieved when IL-1β, IL-6, and TNF-β were added to macrophages with cross-linked costimulatory molecules. Contact between activated lymphocytes and macrophages is necessary to down-regulate inhibitory C/EBPβ, thereby derepressing the HIV-1 LTR. Lymphocyte-derived cytokines activate NF-κB, further enhancing the HIV-1 LTR.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Maximal HIV-1 Replication in Alveolar Macrophages during Tuberculosis Requires both Lymphocyte Contact and Cytokines

Nakata

The Journal of Experimental Medicine

et al. 2002

116

“…C/EBPb, ®rst identi®ed as a positive transcription factor binding to the IL-6 promoter [7], has also been reported to increase the transcriptional activity of viral enhancers like the HIV type 1 LTR (long terminal repeat) [21,22]. In this study, we have investigated the effect of different isoforms of C/ EBPb on the transcriptional regulation of the HPV16 LCR.…”

Section: Discussionmentioning

confidence: 99%

“…C/EBPb recognizes and binds the consensus sequence (5 H TT/GNNGNAAT/ G3 H ) present in the regulatory regions of several acute-phase protein genes and cytokine genes (such as IL6, G-CSF, TNF, and IL8) [7,12,18,19]. Furthermore, C/EBPb is also able to bind to and modulate the enhancers of simian virus 40 (SV40), polyomavirus, and human immunode®ciency virus type 1 (HIV-1) suggesting that C/EBPb is also involved in the regulation of the gene expression of these viruses [7,21,22]. LIP (liver enriched inhibitory protein) probably generated by translation initiation at the third AUG within the same reading frame as LAP lacks the transactivation domain of C/EBPb and acts as a C/EBPb antagonist [10].…”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of human papillomavirus type 16 LCR by different C/EBP? isoforms

et al. 2000

During genital human papillomavirus (HPV) infection several cytokines are released, such as interleukin-1 (IL-1), tumor necrosis factoralpha (TNFalpha), IL-6, and IL-8. These cytokines may play a role in the immune surveillance against viral infection. Two of these cytokines, IL-1 and TNFalpha, suppress the transcription of the HPV16 early genes. CAATT/ enhancer binding protein, (C/EBPbeta), which is activated by IL-1 and TNFalpha, has been suggested to act as a mediator of this transcriptional downregulation. C/EBPbeta contains three different translation initiation sites that can lead probably by leaky ribosome scanning to the generation of three isoforms of C/EBPbeta, namely full-length C/EBPbeta, liver enriched transcriptional activator protein (LAP), and liver enriched inhibitory protein (LIP). When transiently expressed in C33A and HeLa cells, the first two C/EBPbeta isoforms activate the HPV16 long control region (LCR). LIP, which acts as an antagonist of C/EBPbeta, represses the HPV16 LCR activity. Our observation that treatment of HeLa cells with IL-1 leads to induction of LIP supports the hypothesis that the LCR downregulation by IL-1 is mediated by LIP.

“…Studies of other viral enhancers have implicated C/EBP ␤ in regulating the enhancer activities of simian virus 40, polyomavirus, and human immunodeficiency virus type 1 (1). More recently, C/EBP ␤ (NF-IL6) was shown to be a key activator of the human immunodeficiency virus type 1 long terminal repeat (23). Altogether, C/EBP ␤ is an essential cellular transcription factor that seems to be intimately involved in viral gene expression.…”

Section: Discussionmentioning

confidence: 99%

A novel C/EBP beta-YY1 complex controls the cell-type-specific activity of the human papillomavirus type 18 upstream regulatory region

Bauknecht

See

Shi

1996

J Virol

The human papillomavirus type 18 (HPV-18) upstream regulatory region (URR) controls viral gene transcription in a cell-type-specific manner. The HPV-18 URR is active in HeLa cells but inactive in HepG2 cells. The activating activity of YY1 in HeLa cells is dependent on its functional interactions with the switch region which is critical for the HPV-18 URR activity in HeLa cells. Here, we show that a protein complex composed of C/EBP ␤ and YY1 binds the switch region which is detected only in HeLa cells, not in HepG2 cells. Transfection of C/EBP ␤ into HepG2 cells restored the formation of the C/EBP ␤-YY1-switch region complex, accompanied by increased transcription directed by the HPV-18 URR. Mutations in the switch region that abolished the complex formation also abrogated C/EBP ␤-induced transcriptional activation. This provides a strong correlation between the binding of the C/EBP ␤-YY1 complex to the switch region and cell-type-specific URR activity. Taken together, we have identified a novel C/EBP ␤-YY1 complex that binds the switch region and contributes to cell-type-specific HPV-18 URR activity.