Endoplasmic reticulum stress is induced and modulated by enterovirus 71

Jheng, Jia-Rong; Lau, Kean Seng; Tang, Wen-Fang; Wu, Ming-Sian; Horng, Jim-Tong

doi:10.1111/j.1462-5822.2010.01434.x

Cited by 71 publications

(79 citation statements)

References 70 publications

(181 reference statements)

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“…40,41,49,50 Viruses exploit the translational machinery of the host cell to synthesize their viral proteins, leading to increased folding pressure on the ER and chaperone upregulation. 51,52 Thus, it is likely that the adaptive and proapoptotic pathways of UPR are involved in the pathophysiology of viral myocarditis. Furthermore, Mao et al demonstrated that ER stress plays an important role in cardiomyocyte apoptosis and the development of dilated cardiomyopathy in rabbits immunized with a peptide corresponding to the ␤1-aderenoceptor.…”

Section: Cardiac Hypertrophy and Failurementioning

confidence: 99%

Endoplasmic Reticulum Stress As a Therapeutic Target in Cardiovascular Disease

Minamino

Komuro

Kitakaze

2010

Circulation Research

432

347

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Cardiovascular disease constitutes a major and increasing health burden in developed countries.Although treatments have progressed, the development of novel treatments for patients with cardiovascular diseases remains a major research goal. The endoplasmic reticulum (ER) is the cellular organelle in which protein folding, calcium homeostasis, and lipid biosynthesis occur. Stimuli such as oxidative stress, ischemic insult, disturbances in calcium homeostasis, and enhanced expression of normal and/or folding-defective proteins lead to the accumulation of unfolded proteins, a condition referred to as ER stress. ER stress triggers the unfolded protein response (UPR) to maintain ER homeostasis. The UPR involves a group of signal transduction pathways that ameliorate the accumulation of unfolded protein by increasing ER-resident chaperones, inhibiting protein translation and accelerating the degradation of unfolded proteins. The UPR is initially an adaptive response but, if unresolved, can lead to apoptotic cell death. Thus, the ER is now recognized as an important organelle in deciding cell life and death. There is compelling evidence that the adaptive and proapoptotic pathways of UPR play fundamental roles in the development and progression of cardiovascular diseases, including heart failure, ischemic heart diseases, and atherosclerosis. Thus, therapeutic interventions that target molecules of the UPR component and reduce ER stress will be promising strategies to treat cardiovascular diseases. In this review, we summarize the recent progress in understanding UPR signaling in cardiovascular disease and its related therapeutic potential. Future studies may clarify the most promising molecules to be investigated as targets for cardiovascular diseases. (Circ Res. 2010;107:1071-1082.) Key Words: heart failure Ⅲ ischemic heart diseases Ⅲ atherosclerosis Ⅲ ER stress Ⅲ unfolded protein response A lthough the clinical management of heart failure has advanced substantially, 1 and prevention strategies for atherosclerosis focused on managing the established risk factors have progressed markedly, 2 cardiovascular disease still constitutes a major and increasing health burden in developed countries. Thus, the development of novel treatments for patients with cardiovascular diseases remains a major research priority.The endoplasmic reticulum (ER) comprises a complex membranous network found in all eukaryotic cells. It plays a crucial role in the folding of secretory and membrane proteins, calcium homeostasis, and lipid biosynthesis. 3-5 ER Original

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Section: Cardiac Hypertrophy and Failurementioning

confidence: 99%

Endoplasmic Reticulum Stress As a Therapeutic Target in Cardiovascular Disease

Minamino

Komuro

Kitakaze

2010

Circulation Research

432

347

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“…Because many picornaviruses can induce ER stress [29, 30] and this ER stress induces autophagy [31–33], EMCV might cause ER stress and therefore induce autophagy. To test this hypothesis, we analyzed whether the marker molecules of the ER stress were regulated in BHK-21 cells by EMCV infection, 2C or 3D protein expression or thapsigargin (Tg) treatment (as a positive control), which is a known ER stress inducer [34].…”

Section: Resultsmentioning

confidence: 99%

“…Although studies showed that many picornaviruses induce autophagy by activating ER stress [29, 30], a question remains as to whether the underlying mechanisms of EMCV and 2C or 3D protein-induced autophagy are related to ER stress. Thus, the activation of the ER stress pathway was analyzed in BHK-21 cells infected with EMCV, expressed 2C or 3D protein or treated with Tg (as a positive control) (Figure 3).…”

Section: Discussionmentioning

confidence: 99%

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Nonstructural proteins 2C and 3D are involved in autophagy as induced by the encephalomyocarditis virus

Hou

Xin

et al. 2014

Virol J

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BackgroundEncephalomyocarditis virus (EMCV) can infect a variety of animal species and humans. Although the EMCV infection is known to induce autophagy to promote its replication in host cells, the viral proteins that are responsible for inducing autophagy are unknown.MethodsThe recombinant plasmids that were expressing the EMCV proteins were constructed to analyze the role of each protein in the induction of autophagy. Autophagy inductions by the EMCV proteins in BHK-21 cells were investigated by confocal microscopy, Western blotting and transmission electron microscopy. ER stress in BHK-21 cells was examined by detecting the marker molecules using western blotting and luciferase assays.ResultsThis study presents the first demonstration that the nonstructural proteins 2C or 3D of EMCV were involved in inducing autophagy in BHK-21 cells that were expressing 2C or 3D, and we found that inhibiting Beclin1 expression influenced this autophagy induction process. Next, 2C and 3D were shown to be involved in inducing autophagy by activating the ER stress pathway. Finally, EMCV 2C or 3D were demonstrated to regulate the proteins associated with PERK and ATF6alpha pathway.ConclusionsOur findings indicate that 2C and 3D are involved in EMCV-induced autophagy by activating ER stress molecules and regulating the proteins expression associated with UPR pathway, helping to better understand the EMCV-induced autophagy process.Electronic supplementary materialThe online version of this article (doi:10.1186/1743-422X-11-156) contains supplementary material, which is available to authorized users.

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“…Coxackievirus A9 infection of permissive cells requires GRP78 and major histocompatibility complex class I molecules, which are essential for virus internalization (25). It has been reported that the expression of GRP78 is activated by an enterovirus 71-dependent mechanism and that enterovirus 71 infection induces ER stress, but modifies the outcome to assist viral replication (26). …”

Section: Methodsmentioning

confidence: 99%

Glucose-regulated protein 78 is an antiviral against hepatitis A virus replication

Jiang

Haga

Sasaki

et al. 2017

Experimental and Therapeutic Medicine

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Infection with hepatitis A virus (HAV) is a major cause of acute hepatitis globally and it is important to identify the mechanisms of HAV replication. Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum (ER) chaperone and serves a role in unfolded protein response pathways. Previous studies have demonstrated that GRP78 functions as an endogenous antiviral factor. In the present study, two loss-of-function studies using GRP78 were completed to elucidate the role of GRP78 in HAV infection. HAV replication was observed to be enhanced by deficient GRP78 although GRP78-deficiency also led to lower expression of ER stress molecules downstream of GRP78. Therefore, GRP78 appears to be a potential novel defensive molecule against HAV in hepatocytes.

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Endoplasmic reticulum stress is induced and modulated by enterovirus 71

Cited by 71 publications

References 70 publications

Endoplasmic Reticulum Stress As a Therapeutic Target in Cardiovascular Disease

Endoplasmic Reticulum Stress As a Therapeutic Target in Cardiovascular Disease

Nonstructural proteins 2C and 3D are involved in autophagy as induced by the encephalomyocarditis virus

Glucose-regulated protein 78 is an antiviral against hepatitis A virus replication

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