Both ERK1 and ERK2 Are Required for Enterovirus 71 (EV71) Efficient Replication

Zhu, Meng; Duan, Hao; Gao, Meng; Zhang, Hao; Peng, Yiru

doi:10.3390/v7031344

Cited by 23 publications

(19 citation statements)

References 35 publications

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“…c-Myc activation itself can be regulated by MAPK-mediated phosphorylation [64]. Intriguingly, EV71 infection results in MAPK phosphorylation [32,65,66]. It is likely that the MAPK signaling pathway may be involved in upregulation of expression and/or activation of CAD.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Reprogramming of Host Cells in Response to Enteroviral Infection

Cheng

Chien

Lai

et al. 2020

Cells

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Enterovirus 71 (EV71) infection is an endemic disease in Southeast Asia and China. We have previously shown that EV71 virus causes functional changes in mitochondria. It is speculative whether EV71 virus alters the host cell metabolism to its own benefit. Using a metabolomics approach, we demonstrate that EV71-infected Vero cells had significant changes in metabolism. Glutathione and its related metabolites, and several amino acids, such as glutamate and aspartate, changed significantly with the infectious dose of virus. Other pathways, including glycolysis and tricarboxylic acid cycle, were also altered. A change in glutamine/glutamate metabolism is critical to the viral infection. The presence of glutamine in culture medium was associated with an increase in viral replication. Dimethyl α-ketoglutarate treatment partially mimicked the effect of glutamine supplementation. In addition, the immunoblot analysis revealed that the expression of glutamate dehydrogenase (GDH) and trifunctional carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) increased during infection. Knockdown of expression of glutaminase (GLS), GDH and CAD drastically reduced the cytopathic effect (CPE) and viral replication. Furthermore, we found that CAD bound VP1 to promote the de novo pyrimidine synthesis. Our findings suggest that virus may induce metabolic reprogramming of host cells to promote its replication through interactions between viral and host cell proteins.

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Section: Discussionmentioning

confidence: 99%

Metabolic Reprogramming of Host Cells in Response to Enteroviral Infection

Cheng

Chien

Lai

et al. 2020

Cells

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“…Increased ERK1 protein levels are associated with tumour progression and prognosis in gastric cancer . Additionally, a recent study suggested that both ERK1 and ERK2 were involved in the persistent efficient replication of enterovirus 71 . Thus, the interactions between the specific ERK isoforms and Smad2/3 signalling are intricate and not yet fully understood.…”

Section: Discussionmentioning

confidence: 99%

Crosstalk between Smad2/3 and specific isoforms of ERK in TGF‐β1‐induced TIMP‐3 expression in rat chondrocytes

Zhu

et al. 2017

J Cellular Molecular Medi

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This study investigated the roles of ERK1 and ERK2 in transforming growth factor‐β1 (TGF‐β1)‐induced tissue inhibitor of metalloproteinases‐3 (TIMP‐3) expression in rat chondrocytes, and the specific roles of ERK1 and ERK2 in crosstalk with Smad2/3 were investigated to demonstrate the molecular mechanism of ERK1/2 regulation of TGF‐β1 signalling. To examine the interaction of specific isoforms of ERK and the Smad2/3 signalling pathway, chondrocytes were infected with LV expressing either ERK1 or ERK2 siRNA and stimulated with or without TGF‐β1. At indicated time‐points, TIMP‐3 expression was determined by real‐time PCR and Western blotting; p‐Smad3, nuclear p‐Smad3, Smad2/3, p‐ERK1/2 and ERK1/2 levels were assessed. And then, aggrecan, type II collagen and the intensity of matrix were examined. TGF‐β1‐induced TIMP‐3 expression was significantly inhibited by ERK1 knock‐down, and the decrease in TIMP‐3 expression was accompanied by a reduction of p‐Smad3 in ERK1 knock‐down cells. Knock‐down of ERK2 had no effect on neither TGF‐β1‐induced TIMP‐3 expression nor the quantity of p‐Smad3. Moreover, aggrecan, type II collagen expression and the intensity of matrix were significantly suppressed by ERK1 knock‐down instead of ERK2 knock‐down. Taken together, ERK1 and ERK2 have different roles in TGF‐β1‐induced TIMP‐3 expression in rat chondrocytes. ERK1 instead of ERK2 can regulate TGF‐β/Smad signalling, which may be the mechanism through which ERK1 regulates TGF‐β1‐induced TIMP‐3 expression.

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“…Fortunately several publications have presented the effectiveness of knock-downs to regulate global ERK activity, allowing to correctly interpreting the data. For example, the production of EV71 viral particles in Rhabdomyoscarcoma cells was shown to be equally diminished by reduction of ERK1 or ERK2 expression (Zhu et al, 2015 ). Here, both siRNAs effectively reduced the global level of active ERKs, despite the fact that these cells seem to express more ERK2.…”

Section: Search For Specific Functions Of Erk Isoformsmentioning

confidence: 99%

ERK1 and ERK2 Map Kinases: Specific Roles or Functional Redundancy?

Buscà

Pouysségur

Lenormand

2016

Front. Cell Dev. Biol.

221

171

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The MAP kinase signaling cascade Ras/Raf/MEK/ERK has been involved in a large variety of cellular and physiological processes that are crucial for life. Many pathological situations have been associated to this pathway. More than one isoform has been described at each level of the cascade. In this review we devoted our attention to ERK1 and ERK2, which are the effector kinases of the pathway. Whether ERK1 and ERK2 specify functional differences or are in contrast functionally redundant, constitutes an ongoing debate despite the huge amount of studies performed to date. In this review we compiled data on ERK1 vs. ERK2 gene structures, protein sequences, expression levels, structural and molecular mechanisms of activation and substrate recognition. We have also attempted to perform a rigorous analysis of studies regarding the individual roles of ERK1 and ERK2 by the means of morpholinos, siRNA, and shRNA silencing as well as gene disruption or gene replacement in mice. Finally, we comment on a recent study of gene and protein evolution of ERK isoforms as a distinct approach to address the same question. Our review permits the evaluation of the relevance of published studies in the field especially when measurements of global ERK activation are taken into account. Our analysis favors the hypothesis of ERK1 and ERK2 exhibiting functional redundancy and points to the concept of the global ERK quantity, and not isoform specificity, as being the essential determinant to achieve ERK function.

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Both ERK1 and ERK2 Are Required for Enterovirus 71 (EV71) Efficient Replication

Cited by 23 publications

References 35 publications

Metabolic Reprogramming of Host Cells in Response to Enteroviral Infection

Metabolic Reprogramming of Host Cells in Response to Enteroviral Infection

Crosstalk between Smad2/3 and specific isoforms of ERK in TGF‐β1‐induced TIMP‐3 expression in rat chondrocytes

ERK1 and ERK2 Map Kinases: Specific Roles or Functional Redundancy?

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