Foot-and-mouth disease virus induces lysosomal degradation of NME1 to impair p53-regulated interferon-inducible antiviral genes expression

Cell Death & Disease
Huanhuan FengHaixue Zheng

Abstract

Nucleoside diphosphate kinase 1 (NME1) is well-known as a tumor suppressor that regulates p53 function to prevent cancer metastasis and progression. However, the role of NME1 in virus-infected cells remains unknown. Here, we showed that NME1 suppresses viral replication in foot-and-mouth disease virus (FMDV)-infected cells. NME1-enhanced p53-mediated transcriptional activity and induction of interferon-inducible antiviral genes expression. FMDV infection decreased NME1 protein expression. The 2B and VP4 proteins were identified as the viral factors that induced reduction of NME1. FMDV 2B protein has a suppressive effect on host protein expression. We measured, for the first time, VP4-induced lysosomal degradation of host protein; VP4-induced degradation of NME1 through the macroautophagy pathway, and impaired p53-mediated signaling. p53 plays significant roles in antiviral innate immunity by inducing several interferon-inducible antiviral genes expression, such as, ISG20, IRF9, RIG-I, and ISG15. VP4 promoted interaction of p53 with murine double minute 2 (MDM2) through downregulation of NME1 resulting in destabilization of p53. Therefore, 5-flurouracil-induced upregulation of ISG20, IRF9, RIG-I, and ISG15 were suppressed by VP4...Continue Reading

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Citations

Dec 12, 2019·Pharmaceutical Research·Anke-Katrin VolzThorsten Lehr
Apr 25, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Jun-Fei ZhangCheng-Xi Wei
Nov 10, 2020·Frontiers in Microbiology·Jiangling PengDan Li
Mar 16, 2021·Frontiers in Immunology·Kangli LiHaixue Zheng

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Methods Mentioned

BETA
transfection
electrophoresis
immunoprecipitation
lipidation
PCR
Assay

Software Mentioned

Quantity One
LaserGene

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