首页|Caspase-8 activation regulates enterovirus D68 infection-induced inflammatory response and cell death

Caspase-8 activation regulates enterovirus D68 infection-induced inflammatory response and cell death

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Enterovirus D68(EV-D68)infection causes severe acute respiratory infection and severe neurological compli-cations,such as acute flaccid myelitis(AFM),in children.However,although EV-D68 has pandemic potential,no effective drugs or vaccines are currently clinically available.Furthermore,EV-D68 infection-induced inflam-matory response and cell death are not fully understood.In this study,we demonstrated that several inflamma-tory cytokines were upregulated in a multiplicity of infection(MOI)dependent manner in EV-D68-infected human rhabdomyosarcoma(RD)cells.Quantitative reverse transcriptase polymerase chain reaction(qRT-PCR)confirmed that tumor necrosis factor-α(TNF-α),interleukin 6(IL-6),C-C motif chemokine ligand-5(CCL-5),and CXC motif chemokine ligand-5(CXCL-5)mRNA levels were highly upregulated after EV-D68 infection.IL-1β processing and maturation mediated by caspase-8 was inhibited by the caspase-8 inhi-bitor Z-IETD-FMK.EV-D68 infection activates caspase-8 to mediate IL-1β maturation and secretion.Additionally,EV-D68 activated cell death-related proteins such as caspase-3,poly(ADP-ribose)polymerase 1(PARP-1),phosphorylation of Mixed Lineage Kinase domain-like protein(pMLKL),and gasdermin E(GSDME).Thus,EV-D68 infection activates caspase-8,which triggers the necroptosis and apoptosis pathways.Overall,our data suggest that caspase-8 activation is associated with the inflammatory response and cell death in EV-D68-infected RD cells.This mechanism represents a novel target for the treatment of EV-D68 infection by inhibiting caspase-8 activation.

Enterovirus D68(EV-D68)Inflammatory responseCell deathCaspase-8

Yuanyuan Zhou、Chongtao Zhang、Yuhan Zhang、Fei Li、Jun Shen

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Children's Hospital of Fudan University,National Children's Medical Center,Shanghai 201100,China

Wuhan Institute of Virology,Chinese Academy of Sciences,Wuhan 430071,China

China National Institute of Food and Drug Control for providing the Fermon strainpBluescriptⅡ SK-vector-EV-D68 15296Shanghai Science and Technology Commission Medical ProjectContagious and Infectious Diseases Specialist AllianceNational Key Research and Development Program of China

AY42653121Y11901300SHDC220213172022YFC2704900

2024

10.1016/j.bsheal.2024.03.003

生物安全与健康 (英文)
中华医学会

生物安全与健康 (英文)

CSTPCD
ISSN：2096-6962
年,卷(期)：2024.6(3)