The role of Misshapen NCK-related kinase (MINK), a novel Ste20 family kinase, in the IRES-mediated protein translation of human enterovirus 71

PLoS Pathogens
Shi Yun LeongJustin Jang Hann Chu

Abstract

Human Enterovirus 71 (EV71) commonly causes Hand, Foot and Mouth Disease in young children, and occasional occurrences of neurological complications can be fatal. In this study, a high-throughput cell-based screening on the serine/threonine kinase siRNA library was performed to identify potential antiviral agents against EV71 replication. Among the hits, Misshapen/NIKs-related kinase (MINK) was selected for detailed analysis due to its strong inhibitory profile and novelty. In the investigation of the stage at which MINK is involved in EV71 replication, virus RNA transfection in MINK siRNA-treated cells continued to cause virus inhibition despite bypassing the normal entry pathway, suggesting its involvement at the post-entry stage. We have also shown that viral RNA and protein expression level was significantly reduced upon MINK silencing, suggesting its involvement in viral protein synthesis which feeds into viral RNA replication process. Through proteomic analysis and infection inhibition assay, we found that the activation of MINK was triggered by early replication events, instead of the binding and entry of the virus. Proteomic analysis on the activation profile of p38 Mitogen-activated Protein Kinase (MAPK) indicated that...Continue Reading

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Citations

Oct 18, 2016·Nature Communications·Kan Xing WuJustin Jang Hann Chu
Aug 16, 2019·Journal of Virology·Autumn C Holmes, Bert L Semler
Jun 20, 2020·Expert Opinion on Therapeutic Targets·Mira LaajalaVarpu Marjomäki
Jan 26, 2018·PloS One·Hsing-I HuangJhao-Yin Lin
Jan 9, 2020·Journal of Biomedical Science·Ming-Chih LaiRobert Y L Wang
Jun 20, 2019·Journal of Biomedical Science·Collins Oduor Owino, Justin Jang Hann Chu
Sep 5, 2021·Cellular & Molecular Immunology·Kaixiang ZhuLinrong Lu
Jan 29, 2019·Antiviral Research·Christian BrechotScott Weaver

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Datasets Mentioned

BETA
KC866983

Methods Mentioned

BETA
gene knockdown
transfection
co-immunoprecipitation
fluorescence microscopy
FCS
Protein Extraction
reverse transcription-PCR
PCR

Software Mentioned

ImageJ Analysis
WCIF ImageJ
ImageJ
Graphpad
NIH ImageJ
ImageJ Gel Analysis

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