Caspase-3 Inhibition Attenuates the Cytopathic Effects of EV71 Infection

Frontiers in Microbiology
Fengmei SongJinghua Yu

Abstract

Previous studies demonstrate that human enterovirus 71 (EV71), a primary causative agent for hand, foot, and mouth disease, activates caspase-3 through the non-structural viral 3C protein to induce host cell apoptosis; however, until now it was unclear how 3C activates caspase-3 and how caspase-3 activation affects viral production. Our results demonstrate that 3C binds caspase-8 and caspase-9 but does not directly bind caspase-3 to activate them, and that the proteolytic activity of 3C is required by the activation of caspase-8, caspase-9, and caspase-3. Inhibition of caspase-3 activity attenuates apoptosis in 3C-transfected cells. Furthermore, caspase-3 inhibitor protects host cells from the cytopathic effect of EV71 infection and prevents cell cycle arrest, which is known to be favored for EV71 viral replication. Inhibition of caspase-3 activity decreases EV71 viral protein expression and viral production, but has no effect on viral entry, replication, even polyprotein translation. Therefore, caspase-3 is exploited functionally by EV71 to facilitate its production, which suggests a novel therapeutic approach for the treatment and prevention of hand, foot, and mouth disease.

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Citations

Sep 2, 2020·The Journal of Microbiology·Wenbo HuoShucheng Hua
Oct 23, 2018·Phytotherapy Research : PTR·Xiangling MengJinghua Yu
Mar 3, 2020·Frontiers in Microbiology·Shuxia ZhangJinghua Yu
Jun 26, 2020·Frontiers in Microbiology·Yalan LaiXiaoyue Chen
Mar 12, 2021·Journal of Cell Science·Jiamin YiHaixue Zheng

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Methods Mentioned

BETA
immunoprecipitation
transfection
fluorescence-activated cell sorting
FACS
Assay
PCR
transfect
electrophoresis
light microscopy
ELISA

Software Mentioned

SPSS
ModFit LT

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis