Inhibition of cyclooxygenase activity blocks cell-to-cell spread of human cytomegalovirus

Jörg Schröer, Thomas Shenk

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Human cytomegalovirus has previously been shown to induce the accumulation of cyclooxygenase-2 RNA, protein, and enzyme activity. High doses of cyclooxygenase inhibitors substantially block viral replication in cultured fibroblasts. However, doses corresponding to the level of drug achieved in the plasma of patients have little effect on the replication of human cytomegalovirus in cultured cells. Here, we demonstrate that two nonsteroidal antiinflammatory drugs, tolfenamic acid and indomethacin, markedly reduce direct cell-to-cell spread of human cytomegalovirus in cultured fibroblasts. The block is reversed by addition of prostaglandin E2, proving that it results from the action of the drugs on cyclooxygenase activity. Because direct cell-to-cell spread likely contributes importantly to pathogenesis of the virus, we suggest that nonsteroidal anti-inflammatory drugs might help to control human cytomegalovirus infections in conjunction with other antiviral treatments.

Original languageEnglish (US)
Pages (from-to)19468-19473
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number49
DOIs
StatePublished - Dec 9 2008

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Cyclooxygenase inhibitors
  • Human cytomegalovirus pathogenesis

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