{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T11:01:46Z","timestamp":1778238106445,"version":"3.51.4"},"reference-count":26,"publisher":"Proceedings of the National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,3,19]]},"abstract":"<jats:p>\n            Cyclooxygenase 2 (COX-2) mRNA, protein, and activity are transiently induced after infection of human fibroblasts with human cytomegalovirus. Prostaglandin E\n            <jats:sub>2<\/jats:sub>\n            , the product of COX-2 activity, is transiently increased by a factor of &gt;50 in cultures of virus-infected fibroblasts. Both specific (BMS-279652, 279654, and 279655) and nonspecific (indomethacin) COX-2 inhibitors can abrogate the virus-mediated induction of prostaglandin E\n            <jats:sub>2<\/jats:sub>\n            accumulation. Levels of COX-2 inhibitors that completely block the induction of COX-2 activity, but do not compromise cell viability, reduce the yield of human cytomegalovirus in human fibroblasts by a factor of &gt;100. Importantly, the yield of infectious virus can be substantially restored by the addition of prostaglandin E\n            <jats:sub>2<\/jats:sub>\n            together with the inhibitory drug. This finding argues that elevated levels of prostaglandin E\n            <jats:sub>2<\/jats:sub>\n            are required for efficient replication of human cytomegalovirus in fibroblasts. COX-2 inhibitors block the accumulation of immediate-early 2 mRNA and protein, but have little effect on the levels of immediate-early 1 mRNA and protein. Viral DNA replication and the accumulation of some, but not all, early and late mRNAs are substantially blocked by COX-2 inhibitors. Elevated levels of prostaglandin E\n            <jats:sub>2<\/jats:sub>\n            apparently facilitate the production of immediate-early 2 protein. The failure to produce normal levels of this critical viral regulatory protein in the presence of COX-2 inhibitors might block normal progression beyond the immediate-early phase of human cytomegalovirus infection.\n          <\/jats:p>","DOI":"10.1073\/pnas.052713799","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:37:36Z","timestamp":1027694256000},"page":"3932-3937","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":193,"title":["Inhibition of cyclooxygenase 2 blocks human cytomegalovirus replication"],"prefix":"10.1073","volume":"99","author":[{"given":"Hua","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103; and Department of Molecular Biology, Princeton University, Princeton, NJ 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