MEK1–ERKs signal cascade is required for the replication of Enterovirus 71 (EV71)

Wang, Bo; Zhang, Hao; Zhu, Meng; Luo, Zhijun; Peng, Yiru

doi:10.1016/j.antiviral.2011.11.001

Cited by 54 publications

(61 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cell lysates from infected cells were incubated with phospho-ERK1/2 (p-ERK1/2) antibody. Consistently with previous report (Wang et al, 2012a;Wong et al, 2005), EV71 infection triggers early transient and late sustained biphasic activation of ERK1/2. As shown in Fig.…”

Section: Scb Blocks Ev71 Propagation By Inhibition Of Mek1-erk Signalsupporting

confidence: 90%

“…5B and C) while silencing MEK2 had little effect (Fig. 5), which was coincide with previous report that MEK1-ERKs signal cascade was required for the replication of EV71 but not MEK2-ERKs signal pathway (Wang et al, 2012a). To further validate whether SCB inhibit the ERK activation by blocking the activation of MEK1, we tested the protein level of p-MEK1 by Western blot.…”

Section: Scb Blocks Ev71 Propagation By Inhibition Of Mek1-erk Signalsupporting

confidence: 76%

“…Inhibition of ERK activation by U0126, a specific inhibitor of MEK1/2, was found to severely impair virus production. A similar reduction in EV71 replication was also observed when MEK1 expression was knockdown using specific siRNAs (Wang et al, 2012a).…”

Section: Introductionsupporting

confidence: 58%

“…Although the antiviral activity of SCB for HIV and HSV has been reported (Lee et al, 2010;Tian et al, 2012), the antiviral activity of SCB on EV71 has not been reported. Activation of the ERK pathway has been shown to be a necessary cellular modification to support EV71 proliferation, and cellular kinase inhibitors targeting ERK signal pathway have been reported to inhibit EV71 replication (Wang et al, 2012a). Here we found that the water extract could block EV71 infection and this activity was associated with its effect on MEK1-ERK activation, thus extending the antiviral spectrum of this plant.…”

Section: Discussionmentioning

confidence: 87%

“…Accumulated evidence has shown the participation of mitogen-activated protein kinases (MAPKs) during viral infections and this pathway can be utilized by many viruses to amplify themselves in host cells (Hunter et al, 1995;Moser and Schultz-Cherry, 2008;Perkins et al, 2002). EV71 infection activates ERK signal pathway, and the activation of ERK was required in causing immunology injury and for virus replication in EV71 infection (Wang et al, 2012a). Inhibition of ERK activation by U0126, a specific inhibitor of MEK1/2, was found to severely impair virus production.…”

Section: Introductionmentioning

confidence: 98%

See 4 more Smart Citations

Saururus chinensis (Lour.) Baill blocks enterovirus 71 infection by hijacking MEK1–ERK signaling pathway

Wang

Chen

et al. 2015

Antiviral Research

View full text Add to dashboard Cite

Section: Scb Blocks Ev71 Propagation By Inhibition Of Mek1-erk Signalsupporting

confidence: 90%

Section: Scb Blocks Ev71 Propagation By Inhibition Of Mek1-erk Signalsupporting

confidence: 76%

Section: Introductionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 98%

See 3 more Smart Citations

Saururus chinensis (Lour.) Baill blocks enterovirus 71 infection by hijacking MEK1–ERK signaling pathway

Wang

Chen

et al. 2015

Antiviral Research

View full text Add to dashboard Cite

miR‐545 promoted enterovirus 71 replication via directly targeting phosphatase and tensin homolog and tumor necrosis factor receptor‐associated factor 6

Ying

Long

et al. 2019

Journal Cellular Physiology

View full text Add to dashboard Cite

Enterovirus 71 (EV71) is a small, nonenveloped icosahedral RNA virus and is the predominant causative pathogen of hand‐foot‐and‐mouth disease. Recently, microRNAs (miRNAs) are reported to play important roles in the pathogenesis of EV71 replication. This study investigated the role of miR‐545 in the EV71 replication and explored the underlying molecular mechanisms. We showed that miR‐545 was upregulated in the EV71‐infected human embryonic kidney (HEK) 293 cells and rhabdomyosarcoma (RD) cells. Overexpression of miR‐545 promoted the viral replication of EV71 and attenuated the inhibitory effects of EV71 on cell viability in HEK293 and RD cells; while knockdown of miR‐545 significantly suppressed the EV71 replication in these two cell lines. Bioinformatics analysis and luciferase reporter assay showed that miR‐545 directly targeted the 3′untranslated region of phosphatase and tensin homolog (PTEN) and tumor necrosis factor receptor‐associated factor 6 (TRAF6) in HEK293 cells. Furthermore, miR‐545 negatively regulated the messenger RNA (mRNA) and protein expression of PTEN and TRAF6. The mRNA and protein expression of PTEN and TRAF6 was also suppressed by EV71 infection, which was attenuated by miR‐545 knockdown in HEK293 cells. Overexpression of PTEN and TRAF6 both suppressed the EV71 replication in HKE293 cells, and also attenuated the enhanced effects of miR‐545 overexpression on the EV71 replication in HEK293 cells. Collectively, our study for the first time showed that miR‐545 had an enhanced effect on the EV71 replication in HEK293 and RD cells. Further mechanistic results indicated that miR‐545 promoted EV71 replication at least partly via targeting PTEN and TRAF6.

show abstract

Rock1 is a novel host dependency factor of human enterovirus A71: Implication as a drug target

Zhao

Chiu

et al. 2022

Journal of Medical Virology

View full text Add to dashboard Cite

Human enterovirus A71 (EV‐A71) is the major causative agent of hand‐foot‐and‐mouth disease (HFMD) commonly associated with severe neurological diseases, particularly in children under 5 years of age. Several investigational therapeutic agents and vaccine candidates are being developed. However, no approved drug against EV‐A71 infection is available, and no proven drug target has been identified. Since host kinases are key regulators of multiple signaling pathways in response to viral infections, here we screened a kinase inhibitor library and identified potent inhibitors against EV‐A71 infection. Among the hits, GSK269962A, a Rho Associated Coiled‐Coil Containing Protein Kinase (Rock) inhibitor with potent antiviral activity, was selected for further analysis. We found that this Rock inhibitor not only efficiently suppressed the replication of EV‐A71 in RD cells, but also in human intestinal organoids, in a dose‐dependent manner. Interestingly, small interfering RNA depletion of Rock1, but not Rock2, significantly restricted viral replication in RD cells, indicating that Rock1 is a novel host dependency factor for EV‐A71 replication and can serve as a target for the development of anti‐EV‐A71 therapeutics.

show abstract

MEK1–ERKs signal cascade is required for the replication of Enterovirus 71 (EV71)

Cited by 54 publications

References 35 publications

Saururus chinensis (Lour.) Baill blocks enterovirus 71 infection by hijacking MEK1–ERK signaling pathway

Saururus chinensis (Lour.) Baill blocks enterovirus 71 infection by hijacking MEK1–ERK signaling pathway

miR‐545 promoted enterovirus 71 replication via directly targeting phosphatase and tensin homolog and tumor necrosis factor receptor‐associated factor 6

Rock1 is a novel host dependency factor of human enterovirus A71: Implication as a drug target

Contact Info

Product

Resources

About