Inhibition of the phosphatidylinositol 3-kinase-Akt pathway enhances gamma-2 herpesvirus lytic replication and facilitates reactivation from latency
Inhibition of the phosphatidylinositol 3-kinase-Akt pathway enhances gamma-2 herpesvirus lytic replication and facilitates reactivation from latency
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DOI：
10.1099/vir.0.015073-0
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发表时间：
2010-02-01
影响因子：
3.8
通讯作者：
Sun, Ren
中科院分区：
文献类型：
--
作者：
Peng, Li;Wu, Ting-Ting;Sun, Ren
细胞信号通路在调节疱疹病毒潜伏期和裂解复制之间的平衡中起关键作用。在这里，我们研究了磷脂酰肌醇3-激酶(PI3K)-Akt通路对两种γ -2疱疹病毒，小鼠γ -疱疹病毒-68 （MHV-68）和人疱疹病毒-8/卡波西肉瘤相关疱疹病毒（HHV-B/KSHV）复制的影响。我们发现MHV-68的新生感染诱导了pi3k依赖性Akt的激活，并且通过化学抑制剂和RNA干扰技术抑制PI3K-Akt通路，MHV-68的裂解复制得到增强。使用Akt抑制剂VIII抑制Akt活性也有助于KSHV从潜伏期重新激活。裂解复制和潜伏期都取决于病毒反激活因子RTA的活性，我们进一步表明RTA的活性通过降低Akt1的表达而增加。这些数据表明，PI3K-Akt通路抑制RTA的活性，从而有助于维持病毒潜伏期并促进肿瘤发生。
Cellular signalling pathways are critical in regulating the balance between latency and lytic replication of herpesviruses. Here, we investigated the effect of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway on replication of two gamma-2 herpesviruses, murine gammaherpesvirus-68 (MHV-68) and human herpesvirus-8/Kaposi's sarcoma-associated herpesvirus (HHV-B/KSHV). We found that de novo infection of MHV-68 induced PI3K-dependent Akt activation and the lytic replication of MHV-68 was enhanced by inhibiting the PI3K-Akt pathway with both chemical inhibitors and RNA interference technology. Inhibiting the activity of Akt using Akt inhibitor VIII also facilitated the reactivation of KSHV from latency. Both lytic replication and latency depend on the activity of viral transactivator RTA and we further show that the activity of RTA is increased by reducing Akt1 expression. The data suggest that the PI3K-Akt pathway suppresses the activity of RTA and thereby contributes to the maintenance of viral latency and promotes tumorigenesis.