Regulation of HIV-1 Gene Expression by Cellular Transcription Factors

Pathobiology ◽  
1992 ◽  
Vol 60 (4) ◽  
pp. 219-224 ◽  
Author(s):  
Premkumar Ready ◽  
Purandar Dasgupta
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Cellular Transcription ◽  
Hiv 1

scholarly journals T Cell Activation and Regulation of HIV-1: Same Effectors with Distinct Outcomes

1999 ◽  
Vol 10 (suppl c) ◽  
pp. 25C-32C ◽  
Author(s):  
Jean-François Fortin ◽  
Benoit Barbeau ◽  
Gilles A Robichaud ◽  
Michel J Tremblay
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Immune System ◽  
Virus Replication ◽  
T Cell Activation ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Nuclear Factor ◽  
Cellular Transcription ◽  
Hiv 1

The molecular mechanisms that regulate the function of the immune system and human immunodeficiency virus type-1 (HIV-1) gene expression are diverse and complicated. However, replication of HIV-1 is controlled by many of the same regulatory signals that play a crucial role in the transcriptional regulation of the immune system. For example, the viral promoter, as is the case for the immune system, is subject to complex regulation by combinations of cellular transcription factors that may quantitatively and/or qualitatively differ depending on cell types (eg, macrophages versus T lymphocytes) and cell states (eg, undifferentiated versus differentiated or quiescent versus activated). The present review discusses the regulation of HIV-1 gene expression by nuclear factor-kappa Band nuclear factor of activated T cells, and proposes that selective interference of these two cellular transcription factors may be a route to abrogate virus replication without disrupting normal cellular functions. A better understanding of the regulation of HIV-1 gene expression is of utmost importance for the design of molecular approaches that will effectively abrogate virus replication and, ultimately, disease progression.

scholarly journals ZBTB2 represses HIV-1 transcription and is regulated by HIV-1 Vpr and cellular DNA damage responses

2021 ◽  
Vol 17 (2) ◽  
pp. e1009364
Author(s):  
James W. Bruce ◽  
Megan Bracken ◽  
Edward Evans ◽  
Nathan Sherer ◽  
Paul Ahlquist
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Transcription Factor ◽  
Histone Deacetylation ◽  
Transcriptional Elongation ◽  
Cellular Transcription Factor ◽  
Dna Damaging Agents ◽  
Atr Kinase ◽  
Cellular Transcription ◽  
Hiv 1

Previously, we reported that cellular transcription factor ZASC1 facilitates DNA-dependent/RNA-independent recruitment of HIV-1 TAT and the cellular elongation factor P-TEFb to the HIV-1 promoter and is a critical factor in regulating HIV-1 transcriptional elongation (PLoS Path e1003712). Here we report that cellular transcription factor ZBTB2 is a novel repressor of HIV-1 gene expression. ZBTB2 strongly co-immunoprecipitated with ZASC1 and was dramatically relocalized by ZASC1 from the cytoplasm to the nucleus. Mutations abolishing ZASC1/ZBTB2 interaction prevented ZBTB2 nuclear relocalization. We show that ZBTB2-induced repression depends on interaction of cellular histone deacetylases (HDACs) with the ZBTB2 POZ domain. Further, ZASC1 interaction specifically recruited ZBTB2 to the HIV-1 promoter, resulting in histone deacetylation and transcription repression. Depleting ZBTB2 by siRNA knockdown or CRISPR/CAS9 knockout in T cell lines enhanced transcription from HIV-1 vectors lacking Vpr, but not from these vectors expressing Vpr. Since HIV-1 Vpr activates the viral LTR by inducing the ATR kinase/DNA damage response pathway, we investigated ZBTB2 response to Vpr and DNA damaging agents. Expressing Vpr or stimulating the ATR pathway with DNA damaging agents impaired ZASC1’s ability to localize ZBTB2 to the nucleus. Moreover, the effects of DNA damaging agents and Vpr on ZBTB2 localization could be blocked by ATR kinase inhibitors. Critically, Vpr and DNA damaging agents decreased ZBTB2 binding to the HIV-1 promoter and increased promoter histone acetylation. Thus, ZBTB2 is recruited to the HIV-1 promoter by ZASC1 and represses transcription, but ATR pathway activation leads to ZBTB2 removal from the promoter, cytoplasmic sequestration and activation of viral transcription. Together, our data show that ZASC1/ZBTB2 integrate the functions of TAT and Vpr to maximize HIV-1 gene expression.

scholarly journals Lack of negative influence on the cellular transcription factors NF-κB and AP-1 by the Nef protein of human immunodeficiency virus type 1

1999 ◽  
Vol 80 (11) ◽  
pp. 2951-2956 ◽  
Author(s):  
Keejung Yoon ◽  
Sunyoung Kim
Keyword(s):  
Human Immunodeficiency Virus ◽  
Transcription Factors ◽  
Cell Lines ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
Negative Effect ◽  
Cellular Transcription ◽  
Hiv 1

In order to investigate the molecular mechanism of the reported negative effect of the Nef protein of human immunodeficiency virus type 1 (HIV-1) on the cellular transcription factors NF-κB and AP-1, human T cell lines (both populations and subclones) expressing the nef gene from HIV-1 clone pNL432 were constructed. Functional expression of the nef gene was confirmed by downregulation of CD4 and MHC class I proteins on the cell surface as measured by fluorescence-activated cell sorter analysis. However, contrary to previous reports, no significant difference was found in the induced level of NF-κB and AP-1 activity between nef + and nef − cell lines upon stimulation by phorbol 12-myristate 13-acetate and phytohaemagglutinin, as measured by transient transfection and electromobility shift assays. These data indicate that the Nef protein does not have a negative effect on the induction of NF-κB and AP-1.

scholarly journals The EHV-1 UL4 protein that tempers viral gene expression interacts with cellular transcription factors

Virology ◽  
2014 ◽  
Vol 449 ◽  
pp. 25-34 ◽  
Author(s):  
Yunfei Zhang ◽  
Robert A. Charvat ◽  
Seong K. Kim ◽  
Dennis J. O’Callaghan
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Cellular Transcription

scholarly journals Extracellular Signal-Regulated Kinase Activity Is Sustained Early during Human Cytomegalovirus Infection

1998 ◽  
Vol 72 (11) ◽  
pp. 9173-9180 ◽  
Author(s):  
Steven M. Rodems ◽  
Deborah H. Spector
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Transcription Factors ◽  
Protein Kinase ◽  
Hcmv Infection ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Extracellular Signal ◽  
Erk Activity ◽  
Cellular Transcription

ABSTRACT Expression of many early viral genes during human cytomegalovirus (HCMV) infection is dependent on cellular transcription factors. Several immediate-early and early viral promoters contain DNA binding sites for cellular factors such as CREB, AP-1, serum response factor, and Elk-1, and these transcription factors can be activated by phosphorylation via the cellular mitogen-activated protein kinase (MAPK) signal transduction cascade. To determine if the extracellular signal-regulated MAPKs, ERK1 and ERK2, play a role in transcription factor activation during infection, we tested for ERK activity during viral infection. We found that HCMV infection resulted in the maintenance of previously activated ERK1 and ERK2 by a mechanism which appears to involve the inhibition of a cellular phosphatase activity. ERK phosphorylation and activity were sustained for at least 8 h after infection, whereas in mock-infected cells, ERK activity steadily declined by 1 h postinfection. The activity of at least one cellular substrate of the ERKs, the protein kinase RSK1, was also maintained during this period. UV inactivation experiments suggested that viral gene expression was required for sustained ERK activity. In turn, activation of the ERKs appeared to be important for viral gene expression, as evidenced by the observed decrease in the transcriptional activity of the HCMV UL112-113 promoter during infection in the presence of the MEK inhibitor PD98059. These data suggest that HCMV utilizes cellular signal transduction pathways to activate viral or cellular transcription factors involved in the control of early viral gene expression and DNA replication.

scholarly journals Nucleosomes and regulation of gene expression. Structure of the HIV-1 5'LTR.

1998 ◽  
Vol 45 (1) ◽  
pp. 209-219 ◽  
Author(s):  
P Widłak ◽  
W T Garrard
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Chromatin Remodeling ◽  
Binding Sites ◽  
Regulation Of Gene Expression ◽  
Dnase I ◽  
Chromatin Assembly ◽  
Hypersensitive Sites ◽  
Hiv 1

Packaging of DNA into chromatin adds complexity to the problem of regulation of gene expression. Nucleosomes affect the accessibility of transcription factors to occupy their binding sites in chromatin of eukaryotic cells. The disruption of nucleosome structure within the enhancer/promoter region of the integrated HIV-1 proviral genome is an instructive example of a chromatin remodeling process during transcriptional activation. To investigate the mechanism responsible for generating nuclease hypersensitive sites that exist in vivo in the promoter/enhancer region of the 5'LTR (long terminal repeat) of integrated HIV-1 we have utilized an in vitro chromatin assembly system with Xenopus oocyte extracts. Chromatin assembly in the presence of Sp1 and NFkappaB transcription factors induces DNase I hypersensitive sites on either side of their binding sites and positions the adjacent nucleosomes. This structure can also be formed in a factor-induced, ATP-dependent chromatin remodeling process and closely resembles the in vivo chromatin structure. The DNase I hypersensitive sites that form within the HIV LTR are probably histone-free and remain after removal of transcription factors.

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