Inhibition of bovine herpesvirus-4 replication by arsenite through downregulation of the extracellular signal-regulated kinase signaling pathway.
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.
Jiang
Shinn-Jong
SJ
Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
Lin
Tsun-Mei
TM
Shi
Guey-Yueh
GY
Eng
Hock-Liew
HL
Chen
Hsiao-Yen
HY
Wu
Hua-Lin
HL
D000818:Animals; D018053:Arsenites / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000821:virology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D006566:Herpesviridae Infections; D026021:Herpesvirus 4, Bovine / Q000187:drug effects / Q000502:physiology*; D017874:Immediate-Early Proteins / Q000187:drug effects / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D015534:Trans-Activators / Q000187:drug effects / Q000235:genetics; D014412:Tumor Virus Infections; D014779:Virus Replication / Q000187:drug effects*
D018053:Arsenites; D004791:Enzyme Inhibitors; C079185:IE2 protein, bovine herpesvirus type 4; D017874:Immediate-Early Proteins; D015534:Trans-Activators; D048049:Extracellular Signal-Regulated MAP Kinases; C015001:arsenite