Hepatitis E viral infection regulates estrogen signaling pathways: Inhibition of the cAMPK-PKA-CREB and PI3K-AKT-mTOR signaling pathways
Hepatitis E viral infection regulates estrogen signaling pathways: Inhibition of the cAMPK-PKA-CREB and PI3K-AKT-mTOR signaling pathways
复制标题
戊型肝炎病毒感染调节雌激素信号通路：抑制 cAMPK-PKA -CREB 和 PI3K-AKT-mTOR 信号通路。
DOI：
10.1002/jmv.26641
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发表时间：
2020-11-10
影响因子：
12.7
通讯作者：
Yu, Wenhai
中科院分区：
文献类型：
--
作者：
Gong, Shilin;Hao, Xianhui;Yu, Wenhai
戊型肝炎病毒（HEV）感染已成为全球关注的问题，孕妇死亡率高，特别是那些在怀孕的第三个月。雌激素在调节机体生理和病理过程中起着重要作用。雌激素通过与雌激素受体（ER）结合而被激活，并通过涉及跨膜ER的途径介导快速信号传导事件。我们以前的研究已经证实，怀孕期间高雌激素水平与高戊型肝炎病毒滴度有关。然而，戊型肝炎病毒感染和雌激素信号通路之间的联系仍然不清楚。在本研究中，通过戊型肝炎病毒感染的雌激素信号通路的调节进行了评估。结果表明，HEV感染显著抑制cAMP-PKA-CREB和PI 3 K-AKT-mTOR信号通路，但不依赖于Ras-Raf-MEK-ERK信号通路。总之，怀孕期间雌激素水平的增加和高度活化的ER α促进了HEV的复制。反过来，HEV复制的加剧抑制ER α表达并抑制cAMP-PKA-CREB和PI 3 K-AKT-mTOR信号通路。
Hepatitis E virus (HEV) infection has become a global concern with high mortality rates among pregnant women, especially those in their third trimester of pregnancy. Estrogen plays an important role in mediating the body, regulating physiological and pathological processes. Estrogen is activated by binding to estrogen receptors (ERs) and mediates rapid signaling events by pathways that involve transmembrane ERs. Our previous study had confirmed that high estrogen levels during pregnancy are associated with high HEV titers. However, the association between HEV infection and estrogen signaling pathways remains unclear. In the present study, the regulation of estrogen signaling pathways by HEV infection was evaluated. Results demonstrated that HEV infection significantly inhibits the cAMP-PKA-CREB and PI3K-AKT-mTOR signaling pathways, but is independent of the Ras-Raf-MEK-ERK signaling pathway. In summary, the increasing estrogen levels and highly activated ER alpha during pregnancy aggravates HEV replication. The exacerbation of HEV replication, in turn, inhibits ER alpha expression and suppresses both cAMP-PKA-CREB and PI3K-AKT-mTOR signaling pathways.