Role of the PI3K‑AKT‑mTOR pathway in hepatitis B virus infection and replication

Xiang,Kunlun; Wang,Bin

doi:10.3892/mmr.2018.8395

Role of the PI3K‑AKT‑mTOR pathway in hepatitis B virus infection and replication

Authors:
- Kunlun Xiang
- Bin Wang
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Affiliations: Key Laboratory of Medical Molecular Virology of The Ministry of Health and The Ministry of Education, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
Published online on: January 8, 2018 https://doi.org/10.3892/mmr.2018.8395
Pages: 4713-4719

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Abstract

The replication of hepatitis B virus (HBV) may be modulated by a variety of cell signaling pathways, including the phosphatidylinositol 3‑kinase (PI3K)‑RAC‑α serine/threonine‑protein kinase (AKT)‑serine/threonine‑protein kinase mTOR (mTOR) pathway. The aim of the present study was to determine the regulatory effects of this pathway on the infection and replication of HBV. The results indicated that the HBV entry process may activate the AKT pathway, as demonstrated by AKT phosphorylation in HBV natural infection. However, inhibition of AKT phosphorylation by short‑term treatment with AKT inhibitors was unable to block HBV entry, which suggested that AKT activation induced by HBV infection is not essential for viral entry process. Prolonged treatment with PI3K‑AKT‑mTOR pathway inhibitors markedly promoted HBV replication in HBV replicating and natural infection models. The PI3K‑AKT‑mTOR pathway was therefore identified to be a negative regulator of HBV replication. These inhibitors enhanced the replication and transcription of HBV in an HBx‑dependent way. The results additionally indicated that a PI3K inhibitor, Ly294002, inhibited the secretion of the small surface antigen of HBV in a PI3K‑AKT‑independent manner. The inhibitor Ly294002 may be used as a tool for the drug development of surface antigen secretion inhibitors.

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