College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
Vet Res. 2011 Apr 14;42(1):57. doi: 10.1186/1297-9716-42-57.
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.
许多病毒已被证实可以控制关键的细胞信号通路，以促进病毒感染。牛疱疹病毒 1 型（BoHV-1）感染是否涉及信号通路尚不清楚。本研究表明，BoHV-1 感染 MDBK 细胞会诱导早期瞬时和晚期持续激活磷脂酰肌醇 3-激酶（PI3K）/Akt 和丝裂原活化蛋白激酶/细胞外信号调节激酶 1/2（MAPK/Erk1/2）信号通路。通过紫外线照射病毒的刺激分析表明，病毒结合和/或进入过程足以触发早期阶段的激活，而晚期阶段的激活则依赖于病毒蛋白的表达。两种途径的双相激活分别被 PI3K 的选择性抑制剂 Ly294002 和 MAPK 激酶（MEK1/2）的 U0126 抑制。此外，用 Ly294002 处理 MDBK 细胞会导致病毒滴度降低 1.5 个对数级，而 U0126 对病毒产生几乎没有影响。此外，Ly294002 的抑制作用主要发生在病毒复制周期的进入后阶段。这是首次揭示 BoHV-1 积极诱导 PI3K/Akt 和 MAPK/Erk1/2 信号通路，PI3K 的激活对于完全有效的复制至关重要，特别是对于进入后阶段。
