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Journal of Virology, January 1999, p. 404-410, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Human Cytomegalovirus Inhibits Transcription of the CC Chemokine MCP-1 Gene

Alec J. Hirsch and Thomas Shenk*

Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544-1014

Received 1 July 1998/Accepted 13 October 1998

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.

* Corresponding author. Mailing address: Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014. Phone: (609) 258-5992. Fax: (609) 258-1708. E-mail: tshenk{at}princeton.edu.

Journal of Virology, January 1999, p. 404-410, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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