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

Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 12/2008; 105(49):19468-73. DOI: 10.1073/pnas.0810740105
Source: PubMed

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 anti-inflammatory 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 anti-viral treatments.

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Available from: Thomas Shenk, Oct 24, 2014
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    • "NSAIDs can pharmacologically target cyclooxygenase (COX) isozymes, COX-1 and COX-2, finally inhibiting the expression of prostaglandin (PG), which is an important proinflammatory mediator of inflammatory response. Previous studies have shown that NSAIDs were able to suppress HSV reactivation in murine trigeminal ganglions (TGs) [14] [15], as well as inhibit the multiplication of some other types of virus in cell lines [16] [17]. In light of these, we suppose that COX might intensify attacks of MD through promoting viral production or enhancing the severity of nerve inflammation. "
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