The human cytomegalovirus-encoded receptor US28 increases the activity of the major immediate-early promoter/enhancer.
The activation of the major immediate-early promoter (MIEP) is a key event in the cytomegalovirus replication cycle and is dependent on cellular transcription factors which are partially activated by viral proteins. Expression of the viral chemokine receptor homolog US28 results in constitutive activation of pro-inflammatory transcription factors that may be involved in the activation of the major immediate-early promoter/enhancer. Using reporter gene assays in human embryonic kidney cells, we found that US28 signaling was responsible for increased major immediate-early promoter/enhancer activity which was independent of beta-chemokine binding. Inhibition of nuclear factor-kappaB (NF-kappaB) only partially blocked the effect of US28, whereas treatment with a specific p38 mitogen activated kinase (MAPK) inhibitor fully abrogated the US28-induced enhancement of promoter activity. Our results suggest that during human cytomegalovirus (HCMV) infection, US28 in epithelial cells transactivates the major immediate-early promoter/enhancer via the activation of p38 MAPK and downstream signaling that partially involves NF-kappaB.
Boomker
Jasper M
JM
Department of Pathology and Laboratory Medicine, Medical Biology Section, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. j.m.boomker@med.umcg.nl
The
T Hauw
TH
de Leij
Lou F M H
LF
Harmsen
Martin C
MC
D019677:Artificial Gene Fusion; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D017781:Genes, Immediate-Early; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011401:Promoter Regions, Genetic; D019707:Receptors, Chemokine / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D016328:NF-kappa B; D019707:Receptors, Chemokine; C411191:US28 receptor, Cytomegalovirus; D014764:Viral Proteins; D008156:Luciferases; D048051:p38 Mitogen-Activated Protein Kinases