Journal article
Synergistic Activation of The Human Cytomegalovirus Major Immediate Early Promoter by Prostaglandin E2 and Cytokines
Experimental lung research, Vol.24(1), pp.3-14
01/01/1998
DOI: 10.3109/01902149809046050
PMID: 9457465
Abstract
Human cytomegalovirus (HCMV) is a common cause of morbidity and mortality in immunosuppressed patients, especially transplant recipients. In this population, infection is frequently due to reactivation of latent virus. The major immediate early promoter of HCMV controls production of immediate early gene products, which are both trans-and cis-active and are responsible for reactivation. Activation of this promoter is therefore a crucial step in regulation of reactivation infection. It is known that there are cAMP-response elements in the HCMV major immediate early promoter. We hypothesized that prostaglandins (PG), like PGE
2
, which are known to increase cAMP, as well as cytokines known to be released during acute inflammation, may be important in the regulation of this promoter and thus in reactivation of HCMV. To examine this, we transected pCAT760, a plastid containing the major immediate early promoter of HCMV upstream of a chloramphenicol acetyltransferase (CAT) gene, into THP-1 cells. These cells were subsequently stimulated with PGE
2
and/or one of a variety of cytokines. We found that PGE
2
, tumor neurosis factor (TNF)-α, and interleukin (IL)-1β each upregulated the HCMV major immediate early promoter. TNF-α, IL-1β, IL-6, and IL-10 were each synergistic or additive with PGE
2
in upregulating the promoter. Since PGE
2
and the cytokines are all products of activated macrophages, we suggest that acute inflammation and macrophage activation may predispose to reactivation of latent HCMV.
Details
- Title: Subtitle
- Synergistic Activation of The Human Cytomegalovirus Major Immediate Early Promoter by Prostaglandin E2 and Cytokines
- Creators
- Joel N KlineG. Matthew HunninghakeBei HeMarty M MonickGary W Hunninghake
- Resource Type
- Journal article
- Publication Details
- Experimental lung research, Vol.24(1), pp.3-14
- Publisher
- Taylor & Francis
- DOI
- 10.3109/01902149809046050
- PMID
- 9457465
- ISSN
- 0190-2148
- eISSN
- 1521-0499
- Language
- English
- Date published
- 01/01/1998
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Occupational and Environmental Health; Internal Medicine
- Record Identifier
- 9984094593302771
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