The serum and glucocorticoid-regulated protein kinases (SGK) stimulate bovine herpesvirus 1 and herpes simplex virus 1 productive infection.
Serum and glucocorticoid-regulated protein kinases (SGK) are serine/threonine protein kinases that contain a catalytic domain resembling other protein kinases: AKT/protein kinase B, protein kinase A, and protein kinase C-Zeta for example. Unlike these constitutively expressed protein kinases, SGK1 RNA and protein levels are increased by growth factors and corticosteroids. Stress can directly stimulate SGK1 levels as well as stimulate bovine herpesvirus 1 (BoHV-1) and herpes simplex virus 1 (HSV-1) productive infection and reactivation from latency suggesting SGK1 can stimulate productive infection. For the first time, we provide evidence that a specific SGK inhibitor (GSK650394) significantly reduced BoHV-1 and HSV-1 replication in cultured cells. Proteins encoded by the three BoHV-1 immediate early genes (bICP0, bICP4, and bICP22) and two late proteins (VP16 and gE) were consistently reduced by GSK650394 during early stages of productive infection. In summary, these studies suggest SGK may stimulate viral replication following stressful stimuli.
School of Veterinary Medicine and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska, Morisson Life Science Center, RM234, Lincoln, NE 68583-09065, USA.
Insun
I
Kook
Oklahoma State University, Center for Veterinary Health Sciences, Department of Veterinary Pathobiology, Stillwater, OK 74078, USA. Electronic address: clint.jones10@okstate.edu.
Clinton
C
Jones
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006566:Herpesviridae Infections / Q000378:metabolism* / Q000821:virology*; D007242:Herpesvirus 1, Bovine / Q000187:drug effects / Q000502:physiology*; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects; D000099184:Serum-Glucocorticoid Regulated Kinases
D001565:Benzoates; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005938:Glucocorticoids; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases; C532254:2-cyclopentyl-4-(5-phenyl-1H-pyrrolo(2,3-b)pyridin-3-yl)-benzoic acid
Bovine herpesvirus 1 (BoHV-1); Herpes simplex virus 1 (HSV-1); Productive infection; Serum and glucocorticoid-regulated protein kinases