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Cell Mol Immunol. 2018 Jan;15(1):48-57. doi: 10.1038/cmi.2017.102. Epub 2017 Oct 23.

PTEN-L promotes type I interferon responses and antiviral immunity.

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Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan 430072, China.
School of Basic Medical Sciences, Wuhan University, Wuhan 430072, China.
Laboratory for Medical Virology, School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.


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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