Beta-actin variant is necessary for Enterovirus 71 replication

Lui, Yan; Lin, Zhiyang; Lee, Jia Jun; Chow, Vincent T. K.; Poh, Chit Laa; Tan, Eng Lee

doi:10.1016/j.bbrc.2013.03.044

Cited by 12 publications

(12 citation statements)

References 26 publications

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“…Hand, foot, and mouth disease (HFMD) is a viral infection that frequently occurs in infants and children. Common symptoms are blisters and flu-like symptoms [1][2][3]. HFMD is caused by several enteroviruses, including coxsackie virus A16 and enterovirus 71 (EV71) [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: EV71 virus reduces Nrf2 activation to promote production of reactive oxygen species in infected cells

Bai

Zhao

et al. 2020

Gut Pathog

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Background: Emerging evidence closely links Enterovirus 71 (EV71) infection with the generation of reactive oxygen species (ROS). Excess ROS results in apoptosis and exacerbates inflammatory reactions. The Keap1-Nrf2 axis serves as an essential oxidant counteracting pathway. Methods: The present study aimed to elucidate the role of the Keap1-Nrf2 pathway in modulating apoptosis and inflammatory reactions triggered by oxidative stress in Vero and RD cells upon EV71 infection. Results: Elevated ROS production was identified in EV71 infected Vero and RD cells. The percentage of dead cells and expression of inflammation-promoting cytokines were increased in these cells. EV71 infected cells also displayed reinforced Keap1 expression and abrogated Nrf2 expression. Keap1 silencing resulted in the downstream aggregation of the Nrf2 protein and heme oxygenase-1 HO-1. Keap1 silencing repressed ubiquitination and reinforced Nrf2 nuclear trafficking. Furthermore, silencing Keap1 expression repressed ROS production, cell death, and inflammatory reactions in EV71 infected RD and Vero cells. In contrast, silencing of both Keap1 and Nrf2 restored ROS production, cell death, and inflammatory reactions. Nrf2 and Keap1 modulated the stimulation of the Akt sensor and extrinsic as well as intrinsic cell death pathways, resulting in EV71-triggered cell death and inflammatory reactions. Conclusions: EV71 infection can trigger ROS production, cell death, and inflammatory reactions by modulating the Nrf2 and Keap1 levels of infected cells.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: EV71 virus reduces Nrf2 activation to promote production of reactive oxygen species in infected cells

Bai

Zhao

et al. 2020

Gut Pathog

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“…It is composed of 478 amino acids and belongs to the CD36 family ( Yamayoshi et al 2012 ). SCARB2 is commonly found in abundant in the lysosomal membrane of the cell and assist in the internalisation of EV71 into the host cell via clathrin mediated endocytosis ( Hussain et al 2011 ; Lui et al 2013 ; Yamayoshi et al 2012 ). The presence of SCARB2 in HT29 further supports HT29 cells as a viable in vitro model to study EV71 pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, Hussain et al ( 2011 ) has demonstrated that the cytoskeletal system comprising of both actin and microtubules were involved endocytic kinetics ( Buss et al 2001 ; Durrbach et al 1996 ; Flanagan and Lin 1980 ; Hussain et al 2011 ). The knockdown of genes involves in cytoskeleton formation such as ARPC5, ARRB1, and WASF1 and the use of drug disrupting the cytoskeleton network such as cytochalasin B, have resulted in the decrease in EV71 replication kinetics ( Hussain et al 2011 ; Lui et al 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Characterisation of enterovirus 71 replication kinetics in human colorectal cell line, HT29

et al. 2013

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Hand, Foot and Mouth Disease (HFMD), a contagious viral disease that commonly affects infants and children with blisters and flu like symptoms, is caused by a group of enteroviruses such as Enterovirus 71 (EV71) and coxsackievirus A16 (CA16). However some HFMD caused by EV71 may further develop into severe neurological complications such as encephalitis and meningitis. The route of transmission was postulated that the virus transmit from one person to another through direct contact of vesicular fluid or droplet from the infected or via faecal-oral route. To this end, this study utilised a human colorectal adenocarcinoma cell line (HT29) with epithelioid morphology as an in vitro model for the investigation of EV71 replication kinetics. Using qPCR, viral RNA was first detected in HT29 cells as early as 12 h post infection (hpi) while viral protein was first detected at 48 hpi. A significant change in HT29 cells’ morphology was also observed after 48 hpi. Furthermore HT29 cell viability also significantly decreased at 72 hpi. Together, data from this study demonstrated that co-culture of HT29 with EV71 is a useful in vitro model to study the pathogenesis of EV71.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-2-267) contains supplementary material, which is available to authorized users.

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“…Finally, molecular function analysis indicates that majority of these proteins contribute to nucleic acid binding transcription factor activity (34.7%), structural molecule activity (25%) or binding (22.2%) (S1a Fig). A meta-analysis with other selected proteomic studies of EV71-infected muscle and neuronal cells [13][14][15]17,[27][28][29] revealed minimal overlap between NSC-34, RD and other neuronal cell types with 4 protein candidates only, namely ACTB, TUBB, PDIA3 and ENO1, suggesting that the host-pathogen interactions in NSC-34 cells are unique (S1b Fig). The limited overlap may also be partly explained by differential proteomics approaches.…”

Section: In Silico Analysis Of the Biological Function Of The Host Prmentioning

confidence: 97%

Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis

et al. 2018

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A close relative of poliovirus, enterovirus 71 (EV71) is regarded as an important neurotropic virus of serious public health concern. EV71 causes Hand, Foot and Mouth Disease and has been associated with neurological complications in young children. Our limited understanding of the mechanisms involved in its neuropathogenesis has hampered the development of effective therapeutic options. Here, using a two-dimensional proteomics approach combined with mass spectrometry, we have identified a unique panel of host proteins that were differentially and dynamically modulated during EV71 infection of motor-neuron NSC-34 cells, which are found at the neuromuscular junctions where EV71 is believed to enter the central nervous system. Meta-analysis with previously published proteomics studies in neuroblastoma or muscle cell lines revealed minimal overlapping which suggests unique host-pathogen interactions in NSC-34 cells. Among the candidate proteins, we focused our attention on prohibitin (PHB), a protein that is involved in multiple cellular functions and the target of anti-cancer drug Rocaglamide (Roc-A). We demonstrated that cell surface-expressed PHB is involved in EV71 entry into neuronal cells specifically, while membrane-bound mitochondrial PHB associates with the virus replication complex and facilitates viral replication. Furthermore, Roc-A treatment of EV71-infected neuronal cells reduced significantly virus yields. However, the inhibitory effect of Roc-A on PHB in NSC-34 cells was not through blocking the CRAF/MEK/ERK pathway as previously reported. Instead, Roc-A treated NSC-34 cells had lower mitochondria-associated PHB and lower ATP levels that correlated with impaired mitochondria integrity. In vivo, EV71-infected mice treated with Roc-A survived longer than the vehicle-treated animals and had significantly lower virus loads in their spinal cord and brain, whereas virus titers in their limb muscles were comparable to controls. Together, this study uncovers PHB as the first host factor that is specifically involved in EV71 neuropathogenesis and a potential drug target to limit neurological complications.

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Beta-actin variant is necessary for Enterovirus 71 replication

Cited by 12 publications

References 26 publications

RETRACTED ARTICLE: EV71 virus reduces Nrf2 activation to promote production of reactive oxygen species in infected cells

RETRACTED ARTICLE: EV71 virus reduces Nrf2 activation to promote production of reactive oxygen species in infected cells

Characterisation of enterovirus 71 replication kinetics in human colorectal cell line, HT29

Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis

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