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PTEN-L promotes type I interferon responses and antiviral immunity

Cellular & Molecular Immunology volume 15, pages 48–57 (2018)Cite this article

Abstract

Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a well-known tumor suppressor that acts as a dual-specificity phosphatase and is frequently mutated in human cancer. Our previous work has demonstrated that PTEN also plays a vital role in type I interferon responses and antiviral innate immunity. Recently, a translational variant of PTEN with a long N-terminal extension (PTEN-L) has been discovered that is secreted into the extracellular environment and enters recipient cells, where it exerts a phosphatase function antagonistic to PI3K/Akt signaling and tumorigenesis. In this study, we demonstrate that PTEN-L promotes type I interferon responses and antiviral innate immunity during viral infection in a phosphatase activity-dependent manner. Compared with canonical PTEN, PTEN-L also exerts its antiviral function when it is applied exogenously in protein form. This finding was confirmed in cell cultures and mouse infection models. Furthermore, PTEN-L enhances the responses of both type I interferon and proinflammatory cytokines, thus suggesting that PTEN-L might possess additional functions compared with those of PTEN. Thus, the antiviral function of PTEN-L may open an avenue for the use of PTEN-L in antiviral therapy, particularly in patients with PTEN-deficient tumors.

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Acknowledgements

We thank Dr Hong Wu for providing Pten−/− MEFs and Dr Hongliang Li for Ptenflox/flox mice and Dr Mingzhou Chen for providing VSV as a gift. This work was supported by the National Nature Science Foundation of China (grant 81620108020), the China ‘973’ Basic Research Program (#2013CB911101) and Hubei Provincial Science & Technology Innovation Team grant (#2015CFA009).

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Authors and Affiliations

  1. Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, 430072, China

    Yuanyuan Cao, Hongyun Wang, Zhen Zhang, Yu Chen & Deyin Guo

  2. School of Basic Medical Sciences, Wuhan University, Wuhan, 430072, China

    Liu Yang, Chenlin Li, Xu Yuan, Lang Bu & Lang Chen

  3. Laboratory for Medical Virology, School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China

    Chun-Mei Li & Deyin Guo

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  1. Yuanyuan Cao
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  2. Hongyun Wang
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  3. Liu Yang
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  4. Zhen Zhang
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  5. Chenlin Li
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  6. Xu Yuan
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  9. Yu Chen
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  10. Chun-Mei Li
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  11. Deyin Guo
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Correspondence to Chun-Mei Li or Deyin Guo.

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Cao, Y., Wang, H., Yang, L. et al. PTEN-L promotes type I interferon responses and antiviral immunity. Cell Mol Immunol 15, 48–57 (2018). https://doi.org/10.1038/cmi.2017.102

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