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Inhibition of bovine herpesvirus-4 replication by arsenite through downregulation of the extracellular signal-regulated kinase signaling pathway

  • Original Paper
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Journal of Biomedical Science

Abstract

Infection of bovine arterial endothelial (BAE) cells with bovine herpesvirus-4 (BHV-4) induced biphasic activation of one of the cellular mitogen-activated protein kinase (MAPK) downstream targets, extracellular signal-regulated kinase (ERK). ERK activity reached a maximum within 0.5 h postinfection (h.p.i.), and had declined and returned to basal levels by 2 h.p.i. However, at 18–24 h.p.i., a second phase of increased ERK activation occurred. Treatment of BHV-4-infected BAE cells with either U0126, a potent inhibitor of MAPK/ERK kinase, or arsenite dose-dependently blocked ERK activation and inhibited viral DNA synthesis and viral replication in the culture. Further detailed investigations revealed that transcription of viral immediate-early gene 2 (IE-2), which is required for viral DNA replication, was significantly suppressed by both U0126 and arsenite. These results imply that ERK activation may play a pivotal role in herpesvirus replication, and that inhibition of ERK activation can effectively inhibit viral IE protein synthesis and viral replication.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, 701, Tainan, Taiway (ROC)

    Shinn-Jong Jiang, Guey-Yueh Shi, Hsiao-Yen Chen & Hua-Lin Wu PhD

  2. Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan

    Shinn-Jong Jiang, Tsun-Mei Lin, Guey-Yueh Shi, Hsiao-Yen Chen & Hua-Lin Wu PhD

  3. Department of Medical Technology, College of Medicine, National Cheng Kung University, Tainan

    Tsun-Mei Lin

  4. Department of Pathology, Kaohsiung Medical Center, Chang Gung University and Memorial Hospital, Kaohsiung, Taiwan, ROC

    Hock-Liew Eng

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Jiang, SJ., Lin, TM., Shi, GY. et al. Inhibition of bovine herpesvirus-4 replication by arsenite through downregulation of the extracellular signal-regulated kinase signaling pathway. J Biomed Sci 11, 500–510 (2004). https://doi.org/10.1007/BF02256099

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