The Role of Epidermal Growth Factor Receptor Signaling Pathway during Bovine Herpesvirus 1 Productive Infection in Cell Culture.
The Role of Epidermal Growth Factor Receptor Signaling Pathway during Bovine Herpesvirus 1 Productive Infection in Cell Culture.
复制标题
表皮生长因子受体信号通路在细胞培养中牛疱疹病毒 1 型生产感染过程中的作用
DOI：
10.3390/v12090927
复制
发表时间：
2020-08-24
期刊：
影响因子：
--
通讯作者：
Zhu L
中科院分区：
文献类型：
--
作者：
Qiu W;Chang L;He Y;Zhu L
越来越多的研究表明，表皮生长因子受体（epidermal growth factor receptor， EGFR）信号通路在介导多种病毒进入细胞过程中起着至关重要的作用。在这项研究中，我们报道了牛疱疹病毒1 （BoHV-1）在人肺癌细胞系A549和牛肾（MDBK）细胞中的产生性感染导致EGFR的激活，正如EGFR Tyr1068 （Y1068）磷酸化增加所证明的那样，这反过来在病毒感染中起重要作用。添加时间测定支持病毒在进入后阶段的复制受到EGFR特异性抑制剂吉非替尼的影响。有趣的是，在A549细胞中，EGFR的典型下游效应物磷脂酶C-γ1 （PLC-γ1）和Akt在病毒感染后都被激活，而吉非替尼可以抑制PLC-γ1的激活，而Akt则不能。此外，PLC-γ - 1的化学抑制可抑制A549细胞中的病毒滴度，而Akt的抑制则不起作用。而Akt特异性抑制剂Ly294002可显著降低MDBK细胞的病毒滴度。综上所述，我们的数据表明，PLC-γ -1在A549细胞中部分通过EGFR激活，从而有效地复制，而Akt可以被独立于EGFR的病毒感染刺激，并且对病毒产生性感染不是必需的，这表明Akt以细胞类型依赖的方式调节BoHV-1的复制。这项研究为BoHV-1感染如何激活EGFR信号转导以促进病毒复制提供了新的见解。
Accumulating studies have shown that the epidermal growth factor receptor (EGFR) signaling pathway plays an essential role in mediating cellular entry of numerous viruses. In this study, we report that bovine herpesvirus 1 (BoHV-1) productive infection in both the human lung carcinoma cell line A549 and bovine kidney (MDBK) cells leads to activation of EGFR, as demonstrated by the increased phosphorylation of EGFR at Tyr1068 (Y1068), which in turn plays important roles in virus infection. A time-of-addition assay supported that virus replication at post-entry stages was affected by the EGFR specific inhibitor Gefitinib. Interestingly, both phospholipase C-γ1 (PLC-γ1) and Akt, canonical downstream effectors of EGFR, were activated following virus infection in A549 cells, while Gefitinib could inhibit the activation of PLC-γ1 but not Akt. In addition, virus titers in A549 cells was inhibited by chemical inhibition of PLC-γ1, but not by the inhibition of Akt. However, the Akt specific inhibitor Ly294002 could significantly reduce the virus titer in MDBK cells. Taken together, our data suggest that PLC-γ1 is stimulated in part through EGFR for efficient replication in A549 cells, whereas Akt can be stimulated by virus infection independent of EGFR, and is not essential for virus productive infection, indicating that Akt modulates BoHV-1 replication in a cell type-dependent manner. This study provides novel insights on how BoHV-1 infection activates EGFR signaling transduction to facilitate virus replication.
登录
查看更多内容
影响因子：
--
作者：
Chandrasekaran B;Tyagi A;Sharma AK;Cai L;Ankem M;Damodaran C
通讯作者：
Damodaran C
影响因子：
4.8
作者：
Collier, Justin B.;Whitaker, Ryan M.;Schnellmann, Rick G.
通讯作者：
Schnellmann, Rick G.
影响因子：
21.3
作者：
Lin, SY;Makino, K;Hung, MC
通讯作者：
Hung, MC
影响因子：
6.4
作者：
Cuddington, B. P.;Dyer, A. L.;Mossman, K. L.
通讯作者：
Mossman, K. L.
影响因子：
7.5
作者：
Ladanyi, Marc;Pao, William
通讯作者：
Pao, William