Caspase-3 Inhibition Attenuates the Cytopathic Effects of EV71 Infection

Song, Fang; Yu, Xiaoyan; Zhong, Ting; Wang, Zengyan; Meng, Xiang-Ling; Li, Zhaolong; Zhang, Shuxia; Huo, Wenbo; Liu, Xin; Zhang, Yahong; Zhang, Wenyan; Yu, Jinghua

doi:10.3389/fmicb.2018.00817

Cited by 26 publications

(42 citation statements)

References 42 publications

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“…After CA6 infection, the dying cells showed signs of cellular membrane permeability ( Figure 1E), which is a mark of necroptosis (Abdel-Latif et al, 2006;Cho et al, 2009;He et al, 2009). In contrast, cellular PI staining was not observed after EV71 infection ( Figure 1F), which is more suggestive of apoptosis and is consistent with the findings of previous studies (Chang et al, 2004;Song et al, 2018). Therefore, these results raise the possibility that CA6 might induce cytopathic effects through necroptosis, rather than apoptosis.…”

Section: Ca6 Infection Induces Cytopathic Effects Though the Morpholsupporting

confidence: 88%

“…Given that EV71, a causative agent for typical HFMD, is known to induce an obvious cytopathic effect in RD cells (Chang et al, 2004;Lu et al, 2013;Song et al, 2018), we sought to determine whether CA6, a causative agent for atypical HFMD, also induces a cytopathic effect. At 24 h post infection, CA6 did not cause a statistical decrease in the cell number (data not shown); however, at 36 h post infection, CA6 decreased the cell number from 5.1 ± 0.26 × 10 5 to 3.33 ± 0.23 × 10 5 ( Figure 1A).…”

Section: Ca6 Infection Induces Cytopathic Effects Though the Morpholmentioning

confidence: 99%

“…Besides 2A and 3C proteins, non-structural 3D protein as an RNA-dependent RNA polymerase is responsible for viral genome replication via incorporating nucleotides into RNA strand (Baltimore, 1964). Recently our studies have demonstrated that 3C and 3D exert other roles that affect the life cycle of the virus (Song et al, 2018;Wang Z. et al, 2018).…”

Section: Introductionmentioning

confidence: 97%

“…Furthermore, the pathogenic mechanism of EV71 has been heavily investigated. For example, EV71 has been shown to induce apoptosis that is characterized by cell shrinkage, nuclear condensation, and plasma membrane blebbing in different cell lines (Chang et al, 2004;Lu et al, 2013;Song et al, 2018). EV71-associated apoptosis has also been shown to involve the activation of caspases during viral replication (Chang et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Coxsackievirus A6 Induces Necroptosis for Viral Production

Zhang

Meng

et al. 2020

Front. Microbiol.

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Hand, foot, and mouth disease (HFMD) is a febrile exanthematous disease with typical or atypical symptoms. Typical HFMD is usually caused by enterovirus 71 (EV71) or coxsackievirus A16, while atypical HFMD is usually caused by coxsackievirus A6 (CA6). In recent years, worldwide outbreaks of CA6-associated HFMD have dramatically increased, although the pathogenic mechanism of CA6 is still unclear. EV71 has been established to induce caspase-dependent apoptosis, but in this study, we demonstrate that CA6 infection promotes a distinct pathway of cell death that involves loss of cell membrane integrity. Necrostatin-1, an inhibitor of necroptosis, blocks the cell death induced by CA6 infection, but Z-DEVD-FMK, an inhibitor of caspase-3, has no effect on CA6-induced cell death. Furthermore, CA6 infection up-regulates the expression of the necroptosis signaling molecule RIPK3. Importantly, necrostatin-1 inhibits CA6 viral production, as assessed by its ability to inhibit levels of VP1 protein and genomic RNA and infectious particles. CA6-induced necroptosis is not dependent on the generation of reactive oxygen species; however, viral 3D protein can directly bind RIPK3, which is suggestive of a direct mechanism of necroptosis induction. Therefore, these results indicate that CA6 induces a mechanism of RIPK3-dependent necroptosis for viral production that is distinct from the mechanism of apoptosis induced by typical HFMD viruses.

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Section: Ca6 Infection Induces Cytopathic Effects Though the Morpholsupporting

confidence: 88%

Section: Ca6 Infection Induces Cytopathic Effects Though the Morpholmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Coxsackievirus A6 Induces Necroptosis for Viral Production

Zhang

Meng

et al. 2020

Front. Microbiol.

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“…Cleavage of PARP facilitates cellular disassembly and serves as a marker of apoptosis. 43 It could be inferred that Se@RBV restrained the caspase-3-mediated apoptosis pathway by inhibiting the activation of caspase-8.…”

Section: Restriction On Caspase-3 Activation In Vitromentioning

confidence: 99%

Restriction of H1N1 influenza virus infection by selenium nanoparticles loaded with ribavirin via resisting caspase-3 apoptotic pathway

Lin¹,

Li²,

Gong³

et al. 2018

IJN

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IntroductionRibavirin (RBV) is a broad-spectrum antiviral drug. Selenium nanoparticles (SeNPs) attract much attention in the biomedical field and are used as carriers of drugs in current research studies. In this study, SeNPs were decorated by RBV, and the novel nanoparticle system was well characterized. Madin-Darby Canine Kidney cells were infected with H1N1 influenza virus before treatment with RBV, SeNPs, and SeNPs loaded with RBV (Se@RBV).Methods and resultsMTT assay showed that Se@RBV nanoparticles protect cells during H1N1 infection in vitro. Se@RBV depressed virus titer in the culture supernatant. Intracellular localization detection revealed that Se@RBV accumulated in lysosome and escaped to cytoplasm as time elapsed. Furthermore, activation of caspase-3 was resisted by Se@RBV. Expressions of proteins related to caspase-3, including cleaved poly-ADP-ribose polymerase, caspase-8, and Bax, were downregulated evidently after treatment with Se@RBV compared with the untreated infection group. In addition, phosphorylations of phosphorylated 38 (p38), JNK, and phosphorylated 53 (p53) were inhibited as well. In vivo experiments indicated that Se@RBV was found to prevent lung injury in H1N1-infected mice through hematoxylin and eosin staining. Tunel test of lung tissues present that DNA damage reached a high level but reduced substantially when treated with Se@RBV. Immunohistochemical test revealed an identical result with the in vitro experiment that activations of caspase-3 and proteins on the apoptosis pathway were restrained by Se@RBV treatment.ConclusionTaken together, this study elaborates that Se@RBV is a novel promising agent against H1N1 influenza virus infection.

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Natural Oncolysis of Enterovirus 71 in Antitumor Therapy of Colorectal Cancer

et al. 2023

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Colorectal cancer (CRC) is an intestinal malignant tumor with high morbidity and mortality worldwide. Inoperability or resistanance to radiation and chemotherapy occur in the conventional treatments against CRC. Oncolytic viruses (OVs) are one kind of virus that selectively infects and lyses cancer cells, which is considered to be a new anticancer therapy with biological and immune‐based approaches. Enterovirus 71 (EV71), belonging to the enterovirus genus in the family Picornaviridae, is a single positive‐stranded RNA virus. EV71 is transmitted in a fetal‐oral route and infects gastrointestinal tract in infants. Here, EV71 is exploited to be a novel oncolytic virus in colorectal cancer. It is revealed that EV71 infection can selectively cause colorectal cancer cells cytotoxicity but not primary intestinal epithelial cells. Consistently, EV71 injection significantly inhibits tumor growth in nude mice xenografted colorectal cancer cells. In detail, EV71 infects colorectal cancer cells to repress the expression of Ki67 and B‐cell leukemia 2 (Bcl‐2) leading to the inhibition of cell proliferation, while activating the cleavage of poly‐adenosine diphosphatase‐ribose polymerase and Caspase‐3 protein resulting in the promotion of cell apoptosis. The findings demonstrate the oncolytic feature of EV71 in CRC treatment and may provide a potential clue for clinical anticancer therapy.

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Caspase-3 Inhibition Attenuates the Cytopathic Effects of EV71 Infection

Cited by 26 publications

References 42 publications

Coxsackievirus A6 Induces Necroptosis for Viral Production

Coxsackievirus A6 Induces Necroptosis for Viral Production

Restriction of H1N1 influenza virus infection by selenium nanoparticles loaded with ribavirin via resisting caspase-3 apoptotic pathway

Natural Oncolysis of Enterovirus 71 in Antitumor Therapy of Colorectal Cancer

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