Modulation of interleukin 1 beta gene expression by the immediate early genes of human cytomegalovirus.
The immediate early (IE) genes of human cytomegalovirus (HCMV) can be expressed in monocytes/macrophages and are known to regulate other viral genes. The purpose of these studies was to determine if HCMV IE gene products also modulate expression of a monocyte/macrophage-derived gene, interleukin 1 (IL-1) beta. Steady-state cell-derived IL-1 beta mRNA was increased in lipopolysaccharide (LPS)-stimulated THP-1 cells when transfected with the HCMV IE1 + 2 genes, when compared to cells transfected with a control DNA. LPS-stimulated THP-1 cells also exhibited approximately 30-fold higher IL-1 CAT activity when cotransfected with IE1 + 2 than was observed for the same cells cotransfected with IL-1 CAT and a control plasmid containing the IE promoter alone. LPS increased IL-1 CAT activity in the absence of HCMV genes only twofold. IE1, by itself, increased IL-1 CAT activity in LPS-stimulated cells, whereas, IE2, by itself, caused no change in IL-1 CAT activity. These studies show that the IE1 gene of HCMV can regulate IL-1 beta gene expression. The observations further suggest that some of the inflammatory processes associated with HCMV infection may be due to an effect of HCMV IE genes on cell-derived genes, such as the IL-1 beta gene.
Iwamoto
G K
GK
Department of Medicine, University of Iowa College of Medicine, Iowa City 52242.
Monick
M M
MM
Clark
B D
BD
Auron
P E
PE
Stinski
M F
MF
Hunninghake
G W
GW
D000956:Antigens, Viral / Q000502:physiology*; D003587:Cytomegalovirus / Q000235:genetics*; D005786:Gene Expression Regulation; D005814:Genes, Viral; D006801:Humans; D017874:Immediate-Early Proteins; D007375:Interleukin-1 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics*
D000956:Antigens, Viral; D017874:Immediate-Early Proteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014764:Viral Proteins; C044582:immediate-early proteins, cytomegalovirus