Human cytomegalovirus inhibits transcription of the CC chemokine MCP-1 gene.
In primary human diploid fibroblasts, infection with an unpurified stock of human cytomegalovirus induced accumulation of the CC chemokine MCP-1 in the cell culture medium. By 24 h postinfection, the level of MCP-1 returned to that in uninfected cultures. When cells were infected with UV-inactivated human cytomegalovirus, the induction of MCP-1 was still observed, but no reduction was seen by 24 h postinfection or later. This effect was the result of a decrease in the level of MCP-1 mRNA present within the infected cell. Infection with purified virus revealed that the induction of MCP-1 was due to an activity found in the medium of infected cells; purified virions did not induce the expression of MCP-1. However, infection with purified virions repressed the level of MCP-1 mRNA below that found in uninfected cells. Additionally, infection with human cytomegalovirus prevented the induction of MCP-1 expression by tumor necrosis factor alpha and interleukin-1beta. The CC chemokine receptor encoded by the human cytomegalovirus US28 open reading frame (ORF) did not appear to play a role in this process, since a mutant virus in which the US28 ORF had been deleted downregulated MCP-1 in the same manner.
Hirsch
A J
AJ
Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544-1014, USA.
Shenk
T
T
D018932:Chemokine CCL2 / Q000032:analysis / Q000235:genetics*; D018946:Chemokine CCL5 / Q000235:genetics; D003587:Cytomegalovirus / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016366:Open Reading Frames; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018932:Chemokine CCL2; D018946:Chemokine CCL5; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha