Inhibition of cyclooxygenase 2 blocks human cytomegalovirus replication

• Hua Zhu

  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 08544-1014

• Jian-Ping Cong

  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 08544-1014

• Deborah Yu

  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 08544-1014

• Wade A. Bresnahan

  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 08544-1014

• Thomas E. Shenk

  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 08544-1014

抄録

Cyclooxygenase 2 (COX-2) mRNA, protein, and activity are transiently induced after infection of human fibroblasts with human cytomegalovirus. Prostaglandin E 2 , the product of COX-2 activity, is transiently increased by a factor of >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 2 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 >100. Importantly, the yield of infectious virus can be substantially restored by the addition of prostaglandin E 2 together with the inhibitory drug. This finding argues that elevated levels of prostaglandin E 2 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 2 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.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 99 (6), 3932-3937, 2002-02-26

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1360855569833171072
• NII論文ID: 80015235157
• DOI: 10.1073/pnas.052713799
• ISSN: 10916490
• ISSN: 00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.052713799
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