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 th e cell culture medium. By 24 h postinfection, the level of MCP-1 returned t o that in uninfected cultures. When cells were infected with UV-inactivated human cytomegalovirus, the induction of MCP-1 was still observed, but no r eduction was seen by 24 h postinfection or later. This effect was the resul t 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 du e to an activity found in the medium of infected cells; purified virions di d not induce the expression of MCP-1. However, infection with purified viri ons 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-1 beta. The CC chemokine receptor encoded by the human cytomegalovirus US28 open r eading frame (ORF) did not appear to play a role in this process, since a m utant virus in which the US28 ORF had been deleted downregulated MCP-1 in t he same manner.