Maintenance of cyclic GMP-AMP homeostasis by ENPP1 is involved in pseudorabies virus infection

作者：Wang, Jiang; Lu, Shao-Fang; Wan, Bo; Ming, Sheng-Li; Li, Guo-Li; Su, Bing-Qian; Liu, Jiao-Yang; Wei, Yu-Shuang; Yang, Guo-Yu^*; Chu, Bei-Bei^*

来源：Molecular Immunology, 2018, 95: 56-63.

DOI：10.1016/j.molimm.2018.01.008

• Pseudorabies virus
• Ectonucleotide pyrophosphatase
• phosphodiesterase 1
• Cyclic GMP-AMP
• Interferon beta
• Nuclear factor kappa B
• Interferon regulatory factor 3

In a previous study, we demonstrated that porcine cyclic GMP-AMP (cGAMP) synthase (cGAS) catalyzes cGAMP production and is an important DNA sensor for the pseudorabies virus (PRV)-induced activation of interferon 13 (IFN-beta). Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) has recently been identified as the hydrolase of cGAMP in rodents, but its role in porcine cells is not clear. Our recent study demonstrated that porcine ENPP1 is responsible for the homeostasis of cGAMP and is critical for PRV infection. Porcine ENPP1 mRNA is predominantly expressed in muscle. PRV infection was enhanced by ENPP1 overexpression and attenuated by silencing of ENPP1. During PRV infection, the activation of IFN-beta and NF-kappa B was reduced in ENPP1 over expressed cells and promoted in ENPP1 knockdown cells. Investigation of the molecular mechanisms of ENPP1 during PRV infection showed that ENPP1 hydrolyzed cGAMP in PRV-infected or cGAMP-transfected cells and inhibited IRF3 phosphorylation, reducing IFN-beta secretion. These results, combined with those for porcine cGAS, demonstrate that ENPP1 acts coordinately with cGAS to maintain the reservoir of cGAMP and participates in PRV infection.

• 出版日期2018-3
• 单位河南农业大学