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Published on: May 27, 2011
Immediate early gene 2 of human cytomegalovirus increases interleukin 2 receptor-alpha gene expression
1Department of Medicine, University of Iowa College of Medicine, Iowa City 52242, USA. lois-geist@uiowa.edu
Insights
Cytomegalovirus (CMV) immediate early 2 (IE2) protein upregulates interleukin-2 receptor-alpha (IL-2R alpha) gene expression by activating a novel binding site on its promoter. This may contribute to organ transplant rejection.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Cytomegalovirus (CMV) immediate early 2 (IE2) gene product is known to upregulate interleukin-2 receptor-alpha (IL-2R alpha) gene expression.
- Understanding the precise mechanism of this upregulation is crucial for comprehending CMV's role in immune responses and transplant outcomes.
Purpose of the Study:
- To identify the specific region within the IL-2R alpha promoter targeted by the CMV IE2 gene product.
- To characterize the functional significance of this regulatory region in response to IE2.
- To elucidate a potential mechanism linking CMV infection to organ transplant rejection.
Main Methods:
- Utilized a series of IL-2R alpha promoter truncations to map the IE2-responsive region.
- Assessed the activity of promoter constructs in the presence of the CMV IE2 gene product.
- Investigated the function of a newly identified DNA sequence using minimal promoter assays.
Main Results:
- Identified a critical IE2-responsive region in the IL-2R alpha promoter between nucleotides -281 and -273.
- This region, previously lacking known transcription factor activity, was sufficient to drive promoter activity in the presence of IE2.
- Deletion of known enhancer elements did not fully abolish IE2-driven promoter activation, highlighting the importance of the novel site.
Conclusions:
- Discovered a novel transcription factor binding site in the IL-2R alpha promoter that is specifically responsive to the CMV IE2 gene product.
- This interaction provides a molecular mechanism for how CMV infection can enhance IL-2R alpha expression.
- Suggests that increased IL-2R alpha expression due to CMV infection may be a contributing factor to organ transplant rejection.
Abstract:
Previously, we demonstrated that the cytomegalovirus (CMV) immediate early 2 (IE2) gene product upregulates interleukin-2 receptor-alpha (IL-2R alpha) gene expression. To further define this effect, we used a series of IL-2R alpha promoter truncations to identify that the primary site of CMV IE2 activity was in the region between -281 and -273 of the IL-2R alpha promoter, an area without known transcription factor activity. Deletion of known transcription factor enhancer elements resulted in a similar decrease in IE2-driven promoter activation. This unique sequence from the IL-2R alpha promoter was shown to drive a minimal promoter in the presence of IE2. These studies identify a new transcription factor binding site in the IL-2R alpha promoter, which may be specifically responsive to the CMV IE2 gene product. These studies also suggest that one mechanism whereby CMV infection may result in organ transplant rejection is through increased IL-2R alpha expression.
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