Beclin1 Binds to Enterovirus 71 3D Protein to Promote the Virus Replication

Enterovirus 71 (EV71) is the main pathogen causing hand-foot-mouth disease (HFMD) in infants and children, which can also lead to severe neurological diseases and even death. Therefore, understanding the replication mechanism of EV71 is of great significance for the prevention and control of EV71-induced diseases. Beclin1 (BECN1, a mammalian homologue of ATG6 in yeast) is an important core protein for the initiation and the normal process of autophagy in cells. In addition to its involvement in autophagy, Beclin1 has also been reported to play an important role in cancer and innate immune signaling pathways. However, the role of Beclin1 in EV71 replication remains elusive. Here, we primarily found that Beclin1 facilitates EV71 replication in human rhabdomyosarcoma (RD) cells and the autophagy was actually induced, but Beclin1 was not significantly affected at either mRNA level or protein level during early EV71 infection. Further studies discovered that Beclin1 could interacts with EV71 non-structural protein 3D mainly through its evolutionary conserved domain (ECD) and coiled-coiled domain (CCD), thus promoting the replication of EV71 in human rhabdomyosarcoma (RD) cells and human astroglioma (U251) cells. Collectively, we reveal a novel regulatory mechanism associated with Beclin1 to promote EV71 replication, thus providing a potential therapeutic target for the prevention and control of EV71-associated diseases.

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Enterovirus 71 Represses Interleukin Enhancer Binding Factor 2 Production and Nucleus Translocation to Antagonize ILF2 Antiviral Effects

10.20944/preprints201910.0161.v1 ◽

2019 ◽

Author(s):

Jing Jin ◽

Wenbiao Wang ◽

Sha Ai ◽

Qi Zhang ◽

Kailang Wu ◽

...

Keyword(s):

Health Hazard ◽

Enterovirus 71 ◽

Ev71 Infection ◽

Structural Protein ◽

Antiviral Effects ◽

Distinct Mechanism ◽

Binding Factor ◽

2B Protein ◽

Rd Cells ◽

Hand Foot Mouth Disease

Enterovirus 71 (EV71) infection hand-foot-mouth disease (HFMD), meningoencephalitis, neonatal sepsis, and even fatal encephalitis in children, thereby representing a serious public health hazard. It is important to determine the mechanisms underlying the regulation of EV71 infection. In this study, we initially reveal that the interleukin enhancer binding factor 2 (ILF2) down-regulates EV71 50% tissue culture infective dose (TCID50), attenuates EV71 plaque formation unit (PFU), thereby repressing EV71 infection. Moreover, we reveal a distinct mechanism by which EV71 antagonizes ILF2-mediated antiviral effects. Chip data analyses show that ILF2 mRNA is reduced upon EV71 infection. Cellular studies indicate that EV71 infection represses ILF2 mRNA expression and protein production in human leukemic monocytes (THP-1) differentiated macrophages and in human rhabdomyosarcoma (RD) cells. Additionally, EV71 non-structural protein 2B interacts with ILF2 in human embryonic kidney (HEK293T) cells. Interestingly, in the presence of EV71 2B, ILF2 is translocated from the nucleus to the cytoplasm and co-localizes with 2B in the cytoplasm. Therefore, we reveal a distinct mechanism by which EV71 antagonizes ILF2-mediated antiviral effects by inhibiting ILF2 expression and promoting ILF2 translocation from the nucleus to cytoplasm through its 2B protein.

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Enterovirus 71 Represses Interleukin Enhancer-Binding Factor 2 Production and Nucleus Translocation to Antagonize ILF2 Antiviral Effects

Viruses ◽

10.3390/v12010022 ◽

2019 ◽

Vol 12 (1) ◽

pp. 22

Author(s):

Jing Jin ◽

Wenbiao Wang ◽

Sha Ai ◽

Weiyong Liu ◽

Yu Song ◽

...

Keyword(s):

Nonstructural Protein ◽

Enterovirus 71 ◽

Ev71 Infection ◽

Health It ◽

Antiviral Effects ◽

Distinct Mechanism ◽

Binding Factor ◽

2B Protein ◽

Rd Cells ◽

Hand Foot Mouth Disease

Enterovirus 71 (EV71) infection causes hand-foot-mouth disease (HFMD), meningoencephalitis, neonatal sepsis, and even fatal encephalitis in children, thereby presenting a serious risk to public health. It is important to determine the mechanisms underlying the regulation of EV71 infection. In this study, we initially show that the interleukin enhancer-binding factor 2 (ILF2) reduces EV71 50% tissue culture infective dose (TCID50) and attenuates EV71 plaque-formation unit (PFU), thereby repressing EV71 infection. Microarray data analyses show that ILF2 mRNA is reduced upon EV71 infection. Cellular studies indicate that EV71 infection represses ILF2 mRNA expression and protein production in human leukemic monocytes (THP-1) -differentiated macrophages and human rhabdomyosarcoma (RD) cells. In addition, EV71 nonstructural protein 2B interacts with ILF2 in human embryonic kidney (HEK293T) cells. Interestingly, in the presence of EV71 2B, ILF2 is translocated from the nucleus to the cytoplasm, and it colocalizes with 2B in the cytoplasm. Therefore, we present a distinct mechanism by which EV71 antagonizes ILF2-mediated antiviral effects by inhibiting ILF2 expression and promoting ILF2 translocation from the nucleus to the cytoplasm through its 2B protein.

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Expert consensus on prevention and control of COVID-19 in the neurological intensive care unit (first edition)

Stroke and Vascular Neurology ◽

10.1136/svn-2020-000409 ◽

2020 ◽

Vol 5 (3) ◽

pp. 242-249

Author(s):

Furong Wang ◽

Jingyi Liu ◽

Ping Zhang ◽

Wen Jiang ◽

Le Zhang ◽

...

Keyword(s):

Risk Assessment ◽

Intensive Care Unit ◽

Intensive Care ◽

Critically Ill ◽

Critically Ill Patients ◽

Prevention And Control ◽

Neurological Diseases ◽

Neurological Intensive Care Unit ◽

Neurological Intensive Care ◽

And Control

During the COVID-19 epidemic, the treatment of critically ill patients has been increasingly difficult and challenging. During the epidemic, some patients with neurological diseases also have COVID-19, which could be misdiagnosed and cause silent transmission and nosocomial infection. Such risk is high in a neurological intensive care unit (NCU). Therefore, prevention and control of epidemic in critically ill patients is of utmost importance. The principle of NCU care should include comprehensive screening and risk assessment, weighing risk against benefits and reducing the risk of COVID-19 transmission while treating patients as promptly as possible.

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Characterization of Critical Functions of Long Non-Coding RNAs and mRNAs in Rhabdomyosarcoma Cells and Mouse Skeletal Muscle Infected by Enterovirus 71 Using RNA-Seq

Viruses ◽

10.3390/v10100556 ◽

2018 ◽

Vol 10 (10) ◽

pp. 556 ◽

Cited By ~ 8

Author(s):

Ying Li ◽

Chao Zhang ◽

Luwei Qin ◽

Dong Li ◽

Guangyuan Zhou ◽

...

Keyword(s):

Skeletal Muscle ◽

Gene Prediction ◽

Expression Profiles ◽

Enterovirus 71 ◽

Differentially Expressed ◽

Ev71 Infection ◽

Rd Cells ◽

Hand Foot Mouth Disease ◽

Second Generation Sequencing ◽

Non Coding Rnas

Enterovirus 71 (EV71) is the main pathogen of severe hand-foot-mouth disease (HFMD). Long non-coding RNAs (lncRNAs) are recognized as pivotal factors during the pathogenesis of viral infection. However, the critical functions of lncRNAs in EV71–host interactions have not been characterized. Here, for the first time, we performed global transcriptome analysis of lncRNA and mRNA expression profiles in EV71-infected human rhabdomyosarcoma (RD) cells and skeletal muscle of mice using second-generation sequencing. In our study, a total of 3801 novel lncRNAs were identified. In addition, 23 lncRNAs and 372 mRNAs exhibited remarkable differences in expression levels between infected and uninfected RD cells, while 104 lncRNAs and 2647 mRNAs were differentially expressed in infected skeletal muscle from neonatal mice. Comprehensive bioinformatics analysis included target gene prediction, lncRNA‑mRNA co-expression network construction, as well as gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis mainly focused on differentially-expressed genes (DEGs). Our results suggest that lncRNAs may participate in EV71 infection-induced pathogenesis through regulating immune responses, protein binding, cellular component biogenesis and metabolism. The present study provides novel insights into the functions of lncRNAs and the possible pathogenic mechanism following EV71 infection.

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