The PI3K/Akt/mTOR pathway is involved in CVB3-induced autophagy of HeLa cells

Chang,Huan; Li,Xin; Cai,Qian; Li,Chunyun; Tian,Lang; Chen,Jia; Xing,Xiaowei; Gan,Yu; Ouyang,Wen; Yang,Zuocheng

doi:10.3892/ijmm.2017.3008

The PI3K/Akt/mTOR pathway is involved in CVB3-induced autophagy of HeLa cells

Authors:
- Huan Chang
- Xin Li
- Qian Cai
- Chunyun Li
- Lang Tian
- Jia Chen
- Xiaowei Xing
- Yu Gan
- Wen Ouyang
- Zuocheng Yang
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Affiliations: Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China, Center for Medical Experiments, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China, Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China, Department of Anesthesiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China
Published online on: May 31, 2017 https://doi.org/10.3892/ijmm.2017.3008
Pages: 182-192
Copyright: © Chang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Recent studies have found that viral myocarditis (VMC) associated with coxsackievirus B3 (CVB3) causes autophagy activation after infection, but the specific mechanism is not clear. The present study demonstrated that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB)/mammalian target of rapamycin (mTOR) signaling pathway participates in CVB3‑induced autophagy. We found that the light chain 3 (LC3)‑Ⅱ/LC3‑I ratio was increased and p62 and p‑mTOR were altered at different times during CVB3 infection. To further assess the effects of this signaling pathway on CVB3 infection and viral replication, we selected 24 h post‑inoculation (h.p.i.) as our research time point to conduct our next study. We inhibited the function of PI3K, Akt1 and mTOR. The outcome showed that inhibition of PI3K with ZSTK474 alleviated autophagy and decreased CVB3 mRNA replication and VP1 expression. Inhibition of mTOR with rapamycin promoted autophagy and viral mRNA replication but did not impact VP1 expression. Inhibition of Akt with MK2206 aggravated autophagy induced by viral infection. In our research, p62 exhibited a decrease at the beginning of infection but then increased as infection time increased. This finding may serve as a clue to elucidate the function of autophagy at different times of infection. However, the details merit further study. In conclusion, our findings suggest that the PI3K/Akt/mTOR signaling pathway participates in the process of autophagy induced by CVB3 infection. This finding may provide a new perspective of CVB3-induced autophagy.

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