Autophagy is induced and supports virus replication in Enterovirus A71-infected human primary neuronal cells

Lin, Jhao-Yin; Huang, Hsing‐I

doi:10.1038/s41598-020-71970-3

Cited by 18 publications

(14 citation statements)

References 59 publications

(56 reference statements)

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“…In addition to the use of autophagosomes, EVs may also utilize components of exosomes to facilitate en bloc transmission of virions to new cells both in vitro and in vivo [ 119 , 122 , 124 , 125 ]. Interestingly, non-lytic cell release may be a major mechanism of spread in the CNS as EV-A71 infection of neuronal cells (derived from human neural stem cells), neuroblastoma IMR-32 cells, or NSC-34 cells induces autophagy, yet shows no apoptosis or cytopathic effect [ 119 , 126 ]. Inhibition of autophagy by 3-MA led to a decrease in viral load in the brain after intracranial injection of EV-A71 in suckling ICR mice, suggesting that targeting autophagy may be a viable option to prevent neurodegeneration [ 127 ].…”

Section: Autophagy In the Ev Life Cyclementioning

confidence: 99%

Return of the Neurotropic Enteroviruses: Co-Opting Cellular Pathways for Infection

Peters

Carette

2021

Viruses

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Enteroviruses are among the most common human infectious agents. While infections are often mild, the severe neuropathogenesis associated with recent outbreaks of emerging non-polio enteroviruses, such as EV-A71 and EV-D68, highlights their continuing threat to public health. In recent years, our understanding of how non-polio enteroviruses co-opt cellular pathways has greatly increased, revealing intricate host–virus relationships. In this review, we focus on newly identified mechanisms by which enteroviruses hijack the cellular machinery to promote their replication and spread, and address their potential for the development of host-directed therapeutics. Specifically, we discuss newly identified cellular receptors and their contribution to neurotropism and spread, host factors required for viral entry and replication, and recent insights into lipid acquisition and replication organelle biogenesis. The comprehensive knowledge of common cellular pathways required by enteroviruses could expose vulnerabilities amenable for host-directed therapeutics against a broad spectrum of enteroviruses. Since this will likely include newly arising strains, it will better prepare us for future epidemics. Moreover, identifying host proteins specific to neurovirulent strains may allow us to better understand factors contributing to the neurotropism of these viruses.

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Section: Autophagy In the Ev Life Cyclementioning

confidence: 99%

Return of the Neurotropic Enteroviruses: Co-Opting Cellular Pathways for Infection

Peters

Carette

2021

Viruses

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“…Microtubule-associated proteins 1A/1B light chain 3B (LC3-II) was detected using Premo™ autophagy sensor LC3-II-GFP according the manufacturer's protocol. After 24 h, the cells were sequentially treated for 48 h. The LC3-GFP proteins were visualized using an Olympus FV500 confocal microscope using the appropriate filters for GFP (488/520 nm) [49]. 4.4.5.…”

Section: Microscopic Identification Of Autophagymentioning

confidence: 99%

Synergistic Interaction between 5-FU and an Analog of Sulforaphane—2-Oxohexyl Isothiocyanate—In an In Vitro Colon Cancer Model

2021

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Combination therapy is based on the beneficial effects of pharmacodynamic interaction (synergistic or additive) between combined drugs or substances. A considerable group of candidates for combined treatments are natural compounds (e.g., isothiocyanates) and their analogs, which are tested in combination with anticancer drugs. We tested the anticancer effect of the combined treatment of isothiocyanate 2-oxohexyl isothiocyanate and 5-fluorouracil in colon and prostate cancer cell lines. The type of interaction was described using the Chou-Talalay method. The cytostatic and cytotoxic activities of the most promising combined treatments were investigated. In conclusion, we showed that combined treatment with 5-fluorouracil and 2-oxohexyl isothiocyanate acted synergistically in colon cancer. This activity is dependent on the cytostatic properties of the tested compounds and leads to the intensification of their individual cytotoxic activity. The apoptotic process is considered to be the main mechanism of cytotoxicity in this combined treatment.

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“…EVA71-infected neuron cells, including mouse motor neuron NSC-34 cells, human neural stem cells, and differentiated neuroblastoma IMR-32 cells, neither exhibit cytopathic effects nor undergo apoptosis. Instead, complete autophagy flux is markedly induced [ 12 , 83 ]. Many EVA71-containing autophagic vesicles can be isolated from the culture supernatant of NSC-34 cells [ 12 ].…”

Section: The Interplay Between Autophagy and Eva71 Replicationmentioning

confidence: 99%

“…Blocking EVA71-induced autophagy using 3-MA attenuates the disease symptoms and decreases the viral load in the brain tissues of the infected mice [ 28 ]. Autophagic vesicles may be involved in the spread of EVA71 to the CNS [ 12 , 83 ]. These reports indicate that autophagy plays a vital role in EVA71-induced neurological injuries.…”

Section: Autophagy Is Involved In Eva71-induced Nervous System Injurymentioning

confidence: 99%

Dysregulated autophagy contributes to the pathogenesis of enterovirus A71 infection

Zhang

2020

Cell Biosci

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Enterovirus A71 (EVA71) infection continues to remain a vital threat to global public health, especially in the Asia–Pacific region. It is one of the most predominant pathogens that cause hand, foot, and mouth disease (HFMD), which occurs mainly in children below 5 years old. Although EVA71 prevalence has decreased sharply in China with the use of vaccines, epidemiological studies still indicate that EVA71 infection involves severe and even fatal HFMD cases. As a result, it remains more fundamental research into the pathogenesis of EVA71 as well as to develop specific anti-viral therapy. Autophagy is a conserved, self-degradation system that is critical for maintaining cellular homeostasis. It involves a variety of biological functions, such as development, cellular differentiation, nutritional starvation, and defense against pathogens. However, accumulating evidence has indicated that EVA71 induces autophagy and hijacks the process of autophagy for their optimal infection during the different stages of life cycle. This review provides a perspective on the emerging evidence that the “positive feedback” between autophagy induction and EVA71 infection, as well as its potential mechanisms. Furthermore, autophagy may be involved in EVA71-induced nervous system impairment through mediating intracranial viral spread and dysregulating host regulator involved self-damage. Autophagy is a promising therapeutic target in EVA71 infection.

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Autophagy is induced and supports virus replication in Enterovirus A71-infected human primary neuronal cells

Cited by 18 publications

References 59 publications

Return of the Neurotropic Enteroviruses: Co-Opting Cellular Pathways for Infection

Return of the Neurotropic Enteroviruses: Co-Opting Cellular Pathways for Infection

Synergistic Interaction between 5-FU and an Analog of Sulforaphane—2-Oxohexyl Isothiocyanate—In an In Vitro Colon Cancer Model

Dysregulated autophagy contributes to the pathogenesis of enterovirus A71 infection

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