Hepatitis E viral infection regulates estrogen signaling pathways: inhibition of the cAMPK-PKA -CREB and PI3K-AKT-mTOR signaling pathways.

Gong, Shilin; Hao, Xianhui; Bi, Yanhong; Yang, Chenchen; Wang, Wenjing; Mickael, Houfack Kenfack; Zhang, Yike; Chen, Shuangfeng; Qian, Zhongyao; Huang, Fen; Wei, Daqiao; Yu, Wenhai

Hepatitis E virus (HEV) infection has become a global concern with high mortality, especially in pregnant women in their third trimester of pregnancy. Estrogen play 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 ERα during pregnancy aggravates HEV replication. The exacerbation of HEV replication, in turn, inhibits ERα expression and suppress both cAMP-PKA-CREB and PI3K-AKT-mTOR signaling pathways. This article is protected by copyright. All rights reserved.