Caspase Activation and Specific Cleavage of Substrates after Coxsackievirus B3-Induced Cytopathic Effect in HeLa Cells

Carthy, Christopher M.; Granville, David J.; Watson, Kathleen A.; Anderson, Daniel R.; Wilson, Janet E.; Yang, Decheng; Hunt, David W. C.; McManus, Bruce M.

doi:10.1128/jvi.72.9.7669-7675.1998

Cited by 161 publications

(70 citation statements)

References 77 publications

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“…Thus we show that UVirradiated virus, incapable of replication, does not trigger late Akt activation. This finding suggests that the observed high level of late-phase activation is dependent on viral gene expression as has been observed previously in CVB3 infection (Luo et al, 2002;Carthy et al, 1998).…”

Section: Discussionsupporting

confidence: 87%

Phosphorylation of PI3K/Akt and MAPK/ERK in an early entry step of enterovirus 71

et al. 2005

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Viruses have been known to subvert the anti-apoptotic pathways of the host cell in order to delay apoptosis. However, the mechanisms utilized by enterovirus 71 (EV71) to mediate anti-apoptotic activity remained undetermined. We observed that EV71 infection induced an early activation of both phosphatidylinositol 3-kinase (PI3K)/Akt and MAPK/ERK signaling pathways. The activity of GSK3beta, a downstream target of these pathways, was negatively regulated by the activation of both MAPK/ERK and PI3K/Akt. The phosphorylation of GSK3 could be inhibited by treatment with the specific inhibitors of MAPK/ERK and PI3K/Akt. Other Akt downstream targets, BAD, caspase-9 and the Forkhead transcription factor (FKHR), were not phosphorylated during the course of infection by EV71. We further demonstrated that infection by UV-irradiated, inactivated virus triggered early Akt activation but was insufficient to trigger late Akt activation. These data suggest that with the phosphorylation of MAPK/ERK and PI3K/Akt the subsequent inactivation of GSK3beta is utilized by EV71 as a potential mechanism to delay host cell apoptosis.

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Section: Discussionsupporting

confidence: 87%

Phosphorylation of PI3K/Akt and MAPK/ERK in an early entry step of enterovirus 71

et al. 2005

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“…To investigate the contribution of caspases to PRRSV-induced apoptosis, cells infected with PRRSV were treated with a broad spectrum caspase inhibitor. This caspase inhibitor significantly suppressed PARP cleavage as well as DNA fragmentation, suggesting that PRRSV-induced apoptosis is also a caspase-mediated process as seen in other viruses, including transmissible gastroenteritis virus and infectious bronchitis virus (Bartz and Emerman, 1999;Carthy et al, 1998;Devireddy and Jones, 1999;Eleouet et al, 1998;Galvan et al, 2000;Liu et al, 2001;Nava et al, 1998).…”

Section: Discussionmentioning

confidence: 83%

Porcine reproductive and respiratory syndrome virus induces apoptosis through a mitochondria-mediated pathway

Lee

Kleiboeker

2007

Virology

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As with a number of other viruses, Porcine reproductive and respiratory syndrome virus (PRRSV) has been shown to induce apoptosis, although the mechanism(s) involved remain unknown. In this study we have characterized the apoptotic pathways activated by PRRSV infection. PRRSV-infected cells showed evidence of apoptosis including phosphatidylserine exposure, chromatin condensation, DNA fragmentation, caspase activation (including caspase-8, 9, 3), and PARP cleavage. DNA fragmentation was dependent on caspase activation but blocking apoptosis by a caspase inhibitor did not affect PRRSV replication. Upregulation of Bax expression by PRRSV infection was followed by disruption of the mitochondria transmembrane potential, resulting in cytochrome c redistridution to the cytoplasm and subsequent caspase-9 activation. A crosstalk between the extrinsic and intrinsic pathways was demonstrated by dependency of caspase-9 activation on active caspase-8 and by Bid cleavage. Furthermore, in this study we provide evidence of the possible involvement of reactive oxygen species (ROS)-mediated oxidative stress in apoptosis induced by PRRSV. Our data indicated that cell death caused by PRRSV infection involves necrosis as well as apoptosis. In summary, these findings demonstrate mechanisms by which PRRSV induces apoptosis and will contribute to an enhanced understanding of PRRSV pathogenesis.

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“…VMC is caused by the direct virus-infected cardiomyocyte injury via necrosis and apoptosis, and virus-induced inflammatory responses [1]. Apoptosis has been suggested to facilitate viral progeny and spread [25,26] HeLa cells were infected with CVB3 at MOI of 10, and then cells were added with LiCl for 24 hours. Cell were stained with Annexin V and 7-AAD and apoptosis was determined by flow cytometry.…”

Section: Discussionmentioning

confidence: 99%

Lithium chloride confers protection against viral myocarditis via suppression of coxsackievirus B3 virus replication

Zhao

Yan

Wang

et al. 2020

Microbial Pathogenesis

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Lithium chloride confers protection against viral myocarditis via suppression of coxsackievirus B3 virus replication, Microbial Pathogenesis, https://doi. Highlights Lithium chloride inhibits coxsackievirus B3 virus replication in vitro and in vivo.Lithium chloride inhibits CVB3 replication via inhibiting virus-induced cell apoptosis.LiCl treatment in vivo obviously alleviated CVB3-induced acute myocarditis. 3 Abstract Viral myocarditis (VMC) is a type of inflammation affecting myocardial cells caused by viral infection and has been an important cause of dilated cardiomyopathy (DCM) worldwide. Type B3 coxsackievirus (CVB3), a non-enveloped positive-strand RNA virus of the Enterovirus genus, is one of most common agent of viral myocarditis. Till now, effective treatments for VMC are lacking due to lack of drugs or vaccine. Lithium chloride (LiCl) is applied in the clinical management of manic depressive disorders. Accumulating evidence have demonstrated that LiCl, also as an effective antiviral drug, exhibited antiviral effects for specific viruses. However, there are few reports of evaluating LiCl's antiviral effect in mice model. Here, we investigated the inhibitory influence of LiCl on the CVB3 replication in vitro and in vivo and the development of CVB3-induced VMC. We found that LiCl significantly suppressed CVB3 replication in HeLa via inhibiting virus-induced cell apoptosis. Moreover, LiCl treatment in vivo obviously inhibited virus replication within the myocardium and alleviated CVB3-induced acute myocarditis. Collectively, our data demonstrated that LiCl inhibited CVB3 replication and negatively regulated virus-triggered inflammatory responses.Our finding further expands the antiviral targets of LiCl and provides an alternative agent for viral myocarditis. Conflict of interestThe authors declare no conflict of interest. Ethical approvalThe animal experiments were performed in accordance with Soochow University institutional guidelines, and the study was approved by the Ethics Committee of Soochow University in written form. Euthanasia of mice was performed by carbon dioxide inhalation with minimum fear, anxiety and pain. HighlightsLithium chloride inhibits coxsackievirus B3 virus replication in vitro and in vivo.

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Caspase Activation and Specific Cleavage of Substrates after Coxsackievirus B3-Induced Cytopathic Effect in HeLa Cells

Cited by 161 publications

References 77 publications

Phosphorylation of PI3K/Akt and MAPK/ERK in an early entry step of enterovirus 71

Phosphorylation of PI3K/Akt and MAPK/ERK in an early entry step of enterovirus 71

Porcine reproductive and respiratory syndrome virus induces apoptosis through a mitochondria-mediated pathway

Lithium chloride confers protection against viral myocarditis via suppression of coxsackievirus B3 virus replication

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