Proteomic analysis of extremely severe hand, foot and mouth disease infected by enterovirus 71

Deng, Li; Jia, Hongling; Liu, Chao-Wu; Xu, Yufen; Mao, Li-Jia; He, Chun-Hui; Yin, Gen-Quan; Jing, Lin; Tao, Jianping; Zhu, Li

doi:10.1186/1471-2334-13-383

Cited by 8 publications

(6 citation statements)

References 28 publications

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“…There have been few studies that demonstrated serum proteins in the extremely severe EV71 patients using 2-DE proteomics analysis. 1 There were 38 differentially expressed spots identified from the serum of extremely severe EV71 patients using 2-DE proteomic approach. A variety of cellular functions were covered by their identified proteins, including infection immunity-related proteins, signaling molecule, metabolic-related proteins.…”

confidence: 99%

“…1,2 Since the late 1990s, large epidemic outbreaks of EV71 that are associated with severe neurological complications and high mortality rates have occurred in Taiwan, Singapore, Japan and other Asian-Pacific areas. [3][4][5][6][7] In 1998, EV71 caused a large-scale epidemic in Taiwan, which led to 405 severe cases and 78 deaths due to the development of neurologic complications such as meningitis and encephalitis.…”

mentioning

confidence: 99%

“…Despite the powerful technology developed to enhance the study on the diagnosis and prevention of human diseases, there is only one article on proteomic analyses of EV71, and the comparative serum proteomic analysis in children with mild and severe EV71 infections has not been reported. 1,18 In this study, we aim to identify potential proteins as biomarkers by comparing proteome map among mild EV71-infected patients, severe EV71-infected patients and healthy control children.…”

mentioning

confidence: 99%

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Proteome Demonstration of Alpha-1-Acid Glycoprotein and Alpha-1-Antichymotrypsin Candidate Biomarkers for Diagnosis of Enterovirus 71 Infection

Wang¹,

Kuo²,

Yen

et al. 2015

Pediatric Infectious Disease Journal

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Proteome Demonstration of Alpha-1-Acid Glycoprotein and Alpha-1-Antichymotrypsin Candidate Biomarkers for Diagnosis of Enterovirus 71 Infection

Wang¹,

Kuo²,

Yen

et al. 2015

Pediatric Infectious Disease Journal

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“…EV-A71 is known for its high infectivity and its ability to mutate rapidly and cause serious illness. Pathological conditions caused by EV-A71 infection include hand-foot-mouth disease, herpes virus, and neurological complications [5,6]. However, a detailed understanding of the pathogenesis of EV-A71 is lacking.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA 876-5p modulates EV-A71 replication through downregulation of host antiviral factors

Cheng

et al. 2020

Virol J

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Background: Human enterovirus 71 (EV-A71) is a non-enveloped virus that has a single stranded positive sense RNA genome. In a previous study, we showed that miR-876-5p upregulation was observed in the serum of patients with severe EV-A71 infection. Micro-876-5p (miR-876-5p) is a circulating miRNA that can be identified to modulate EV-A71 infections through both in vitro and in vivo studies. However, the regulatory mechanisms that involve miR-876-5p in the EV-A71 infection cycle remain unclear. Methods: We demonstrated that miR-876-5p facilitated EV-A71 replication and expression by overexpression and knocking-down of miR-876-5p through the transfection of miR-876-5p plasmid and miR-876-5p inhibitor. Although miR-876-5p suppressed CREB5 expression, luciferase reporter assay confirmed this. We also evaluated the role of miR-876-5p in the EV-A71 infection cycle by CREB5 mediated by transfection with an anti-miR-876-5P inhibitor or in combination with an si-CREB5 plasmid. Results: MicroR-876-5p was upregulated in EV-A71-infected neuroblastoma cells. Overexpression of miR-876-5p or knockdown of cyclic-AMP responsive element binding protein 5 (CREB5) promoted EV-A71 replication. The downregulation of miR-876-5p inhibited the accumulation of viral RNA and the production of viral proteins. Interestingly, CREB5 overexpression also suppressed EV-A71 replication. Our in vitro studies reveal that miR-876-5p directly targets CREB5. Finally, downregulation of CREB5 protein abated the inhibitory effect of anti-miR-876-5p and induced inhibitory effect of EV-A71 replication. Conclusions: Our results suggest that intracellular miR-876-5p promotes EV-A71 replication indirectly by targeting the host CREB5 protein.

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“…The increasing awareness of life-threatening EV71 infections has boosted research in recent years to further understand virus-host interactions and develop effective antiviral strategies [12][13][14][15][16][17]. However, the neuropathogenesis of EV71 is still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis

et al. 2018

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A close relative of poliovirus, enterovirus 71 (EV71) is regarded as an important neurotropic virus of serious public health concern. EV71 causes Hand, Foot and Mouth Disease and has been associated with neurological complications in young children. Our limited understanding of the mechanisms involved in its neuropathogenesis has hampered the development of effective therapeutic options. Here, using a two-dimensional proteomics approach combined with mass spectrometry, we have identified a unique panel of host proteins that were differentially and dynamically modulated during EV71 infection of motor-neuron NSC-34 cells, which are found at the neuromuscular junctions where EV71 is believed to enter the central nervous system. Meta-analysis with previously published proteomics studies in neuroblastoma or muscle cell lines revealed minimal overlapping which suggests unique host-pathogen interactions in NSC-34 cells. Among the candidate proteins, we focused our attention on prohibitin (PHB), a protein that is involved in multiple cellular functions and the target of anti-cancer drug Rocaglamide (Roc-A). We demonstrated that cell surface-expressed PHB is involved in EV71 entry into neuronal cells specifically, while membrane-bound mitochondrial PHB associates with the virus replication complex and facilitates viral replication. Furthermore, Roc-A treatment of EV71-infected neuronal cells reduced significantly virus yields. However, the inhibitory effect of Roc-A on PHB in NSC-34 cells was not through blocking the CRAF/MEK/ERK pathway as previously reported. Instead, Roc-A treated NSC-34 cells had lower mitochondria-associated PHB and lower ATP levels that correlated with impaired mitochondria integrity. In vivo, EV71-infected mice treated with Roc-A survived longer than the vehicle-treated animals and had significantly lower virus loads in their spinal cord and brain, whereas virus titers in their limb muscles were comparable to controls. Together, this study uncovers PHB as the first host factor that is specifically involved in EV71 neuropathogenesis and a potential drug target to limit neurological complications.

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Proteomic analysis of extremely severe hand, foot and mouth disease infected by enterovirus 71

Cited by 8 publications

References 28 publications

Proteome Demonstration of Alpha-1-Acid Glycoprotein and Alpha-1-Antichymotrypsin Candidate Biomarkers for Diagnosis of Enterovirus 71 Infection

Proteome Demonstration of Alpha-1-Acid Glycoprotein and Alpha-1-Antichymotrypsin Candidate Biomarkers for Diagnosis of Enterovirus 71 Infection

MicroRNA 876-5p modulates EV-A71 replication through downregulation of host antiviral factors

Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis

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