title: Biphasic activation of PI3K/Akt and MAPK/Erk1/2 signaling pathways in bovine herpesvirus type 1 infection of MDBK cells.
abstract: Many viruses have been known to control key cellular signaling pathways to facilitate the virus infection. The possible involvement of signaling pathways in bovine herpesvirus type 1 (BoHV-1) infection is unknown. This study indicated that infection of MDBK cells with BoHV-1 induced an early-stage transient and a late-stage sustained activation of both phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen activated protein kinases/extracellular signal-regulated kinase 1/2 (MAPK/Erk1/2) signaling pathways. Analysis with the stimulation of UV-irradiated virus indicated that the virus binding and/or entry process was enough to trigger the early phase activations, while the late phase activations were viral protein expression dependent. Biphasic activation of both pathways was suppressed by the selective inhibitor, Ly294002 for PI3K and U0126 for MAPK kinase (MEK1/2), respectively. Furthermore, treatment of MDBK cells with Ly294002 caused a 1.5-log reduction in virus titer, while U0126 had little effect on the virus production. In addition, the inhibition effect of Ly294002 mainly occurred at the post-entry stage of the virus replication cycle. This revealed for the first time that BoHV-1 actively induced both PI3K/Akt and MAPK/Erk1/2 signaling pathways, and the activation of PI3K was important for fully efficient replication, especially for the post-entry stage.
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. yzgqzhu@yzu.edu.cn.
authors.forename: Liqian
authors.initials: L
authors.lastname: Zhu
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Ding
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Zhu
authors.forename: Songshu
authors.initials: S
authors.lastname: Meng
authors.forename: Jianye
authors.initials: J
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Qiangde
authors.initials: Q
authors.lastname: Duan
authors.forename: Jie
authors.initials: J
authors.lastname: Tao
authors.forename: Dieter M
authors.initials: DM
authors.lastname: Schifferli
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Zhu
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000662:veterinary; D002070:Butadienes / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D006566:Herpesviridae Infections / Q000662:veterinary* / Q000821:virology; D007242:Herpesvirus 1, Bovine / Q000502:physiology*; D007241:Infectious Bovine Rhinotracheitis / Q000821:virology*; D020935:MAP Kinase Signaling System; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics* / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D053585:Virus Attachment
chemical_list: D002070:Butadienes; D002867:Chromones; D009025:Morpholines; D009570:Nitriles; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D058539:Phosphatidylinositol 3-Kinase; D020929:Mitogen-Activated Protein Kinase Kinases