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PTEN Lipid Phosphatase Activity Enhances Dengue Virus Production through Akt/FoxO1/Maf1 Signaling

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Virologica Sinica

Abstract

Dengue virus (DENV) is an arthropod-borne viral pathogen and a global health burden. Knowledge of the DENV-host interactions that mediate virus pathogenicity remains limited. Host lipid metabolism is hijacked by DENV for virus replication in which lipid droplets (LDs) play a key role during the virus lifecycle. In this study, we reveal a novel role for phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in LDs-mediated DENV infection. We demonstrate that PTEN expression is downregulated upon DENV infection through post-transcriptional regulation and, in turn, PTEN overexpression enhances DENV replication. PTEN lipid phosphatase activity was found to decrease cellular LDs area and number through Akt/FoxO1/Maf1 signaling, which, together with autophagy, enhanced DENV replication and virus production. We therefore provide mechanistic insight into the interaction between lipid metabolism and the DENV replication cycle.

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Acknowledgements

This study was funded by the National Natural Science Foundation of China (81171564), the National Key Research and Development Program of China (2016YFC1200400) and the National S&T Major Project for Infectious Diseases Control (2017ZX10304403). The authors thank Yingfeng Lei (Fourth Military Medical University, China) for providing us polyclonal anti-DENV-2 antibodies for immunofluorescence assay.

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  1. Bin Liu, Ting-Ting Gao contributed equally to this work

Authors and Affiliations

  1. Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, 200433, China

    Bin Liu, Ting-Ting Gao, Xiao-Yu Fu, Zhen-Hao Xu, Hao Ren, Ping Zhao, Zhong-Tian Qi & Zhao-Ling Qin

  2. Department of Nephrology, The Air Force Hospital from Northern Theater of PLA, Shenyang 110042, China

    Ting-Ting Gao

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  1. Bin Liu
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Contributions

QZT and QZL designed the experiments. LB, GTT, FXY, XZH carried out the experiments. QZL and LB analyzed the data and wrote the paper. All the authors approved the final manuscript.

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Correspondence to Zhong-Tian Qi or Zhao-Ling Qin.

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Liu, B., Gao, TT., Fu, XY. et al. PTEN Lipid Phosphatase Activity Enhances Dengue Virus Production through Akt/FoxO1/Maf1 Signaling. Virol. Sin. 36, 412–423 (2021). https://doi.org/10.1007/s12250-020-00291-6

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