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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.

Author information

1
Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan 430072, China.
2
School of Basic Medical Sciences, Wuhan University, Wuhan 430072, China.
3
Laboratory for Medical Virology, School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.

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.

PMID:
29057971
PMCID:
PMC5827174
DOI:
10.1038/cmi.2017.102
[Indexed for MEDLINE]
Free PMC Article

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