Pim1 Impacts Enterovirus A71 Replication and Represents a Potential Target in Antiviral Therapy

Fanghang Zhou; Qianya Wan; Jing Lu; Ying Chen; Gui Lu; Ming Liang He

doi:10.1016/j.isci.2019.08.008

Pim1 Impacts Enterovirus A71 Replication and Represents a Potential Target in Antiviral Therapy

Fanghang Zhou
, Qianya Wan
, Jing Lu
, Ying Chen
, Gui Lu
, Ming Liang He^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

22 Citations (Scopus)

90 Downloads (CityUHK Scholars)

Abstract

Enterovirus A71 (EV-A71) infection causes hand-foot-and-mouth disease (HFMD) and fatal neurological diseases, and there are no effective treatments. Host factors play key roles in establishing viral infection and determining the disease progression and outcome of antiviral therapies. In this study, we found that the expression of Pim1 was significantly upregulated in EV-A71 infection. Ectopic expression or silencing of Pim1 promoted or inhibited EV-A71 replication through two distinct mechanisms. Pim1 enhanced viral IRES activity by increasing viral 2A protease-mediated eIF4G cleavage and blocked AUF1, a suppressor of IRES, translocation from the nucleus to cytosol. More importantly, we discovered that Pim1 inhibitors (SGI-1776, AZD-1208, and CX-6258) reduced EV-A71 reproduction. Particularly, CX-6258 remarkably reduced EV-A71 reproduction more than 1,000 times, providing a potential therapeutic agent for EV-A71 treatment.

Original language	English
Pages (from-to)	715-727
Journal	iScience
Volume	19
Online published	8 Aug 2019
DOIs	https://doi.org/10.1016/j.isci.2019.08.008
Publication status	Published - 27 Sept 2019

Research Keywords

Biochemistry
Biological Sciences
Cell Biology
Microbiology
Molecular Microbiology
Viral Microbiology
Virology

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This full text is made available under CC-BY-NC-ND 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/

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title = "Pim1 Impacts Enterovirus A71 Replication and Represents a Potential Target in Antiviral Therapy",

abstract = "Enterovirus A71 (EV-A71) infection causes hand-foot-and-mouth disease (HFMD) and fatal neurological diseases, and there are no effective treatments. Host factors play key roles in establishing viral infection and determining the disease progression and outcome of antiviral therapies. In this study, we found that the expression of Pim1 was significantly upregulated in EV-A71 infection. Ectopic expression or silencing of Pim1 promoted or inhibited EV-A71 replication through two distinct mechanisms. Pim1 enhanced viral IRES activity by increasing viral 2A protease-mediated eIF4G cleavage and blocked AUF1, a suppressor of IRES, translocation from the nucleus to cytosol. More importantly, we discovered that Pim1 inhibitors (SGI-1776, AZD-1208, and CX-6258) reduced EV-A71 reproduction. Particularly, CX-6258 remarkably reduced EV-A71 reproduction more than 1,000 times, providing a potential therapeutic agent for EV-A71 treatment.",

keywords = "Biochemistry, Biological Sciences, Cell Biology, Microbiology, Molecular Microbiology, Viral Microbiology, Virology",

author = "Fanghang Zhou and Qianya Wan and Jing Lu and Ying Chen and Gui Lu and He, \{Ming Liang\}",

year = "2019",

month = sep,

day = "27",

doi = "10.1016/j.isci.2019.08.008",

language = "English",

volume = "19",

pages = "715--727",

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T1 - Pim1 Impacts Enterovirus A71 Replication and Represents a Potential Target in Antiviral Therapy

AU - Zhou, Fanghang

AU - Wan, Qianya

AU - Lu, Jing

AU - Chen, Ying

AU - Lu, Gui

AU - He, Ming Liang

PY - 2019/9/27

Y1 - 2019/9/27

N2 - Enterovirus A71 (EV-A71) infection causes hand-foot-and-mouth disease (HFMD) and fatal neurological diseases, and there are no effective treatments. Host factors play key roles in establishing viral infection and determining the disease progression and outcome of antiviral therapies. In this study, we found that the expression of Pim1 was significantly upregulated in EV-A71 infection. Ectopic expression or silencing of Pim1 promoted or inhibited EV-A71 replication through two distinct mechanisms. Pim1 enhanced viral IRES activity by increasing viral 2A protease-mediated eIF4G cleavage and blocked AUF1, a suppressor of IRES, translocation from the nucleus to cytosol. More importantly, we discovered that Pim1 inhibitors (SGI-1776, AZD-1208, and CX-6258) reduced EV-A71 reproduction. Particularly, CX-6258 remarkably reduced EV-A71 reproduction more than 1,000 times, providing a potential therapeutic agent for EV-A71 treatment.

AB - Enterovirus A71 (EV-A71) infection causes hand-foot-and-mouth disease (HFMD) and fatal neurological diseases, and there are no effective treatments. Host factors play key roles in establishing viral infection and determining the disease progression and outcome of antiviral therapies. In this study, we found that the expression of Pim1 was significantly upregulated in EV-A71 infection. Ectopic expression or silencing of Pim1 promoted or inhibited EV-A71 replication through two distinct mechanisms. Pim1 enhanced viral IRES activity by increasing viral 2A protease-mediated eIF4G cleavage and blocked AUF1, a suppressor of IRES, translocation from the nucleus to cytosol. More importantly, we discovered that Pim1 inhibitors (SGI-1776, AZD-1208, and CX-6258) reduced EV-A71 reproduction. Particularly, CX-6258 remarkably reduced EV-A71 reproduction more than 1,000 times, providing a potential therapeutic agent for EV-A71 treatment.

KW - Biochemistry

KW - Biological Sciences

KW - Cell Biology

KW - Microbiology

KW - Molecular Microbiology

KW - Viral Microbiology

KW - Virology

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DO - 10.1016/j.isci.2019.08.008

M3 - RGC 21 - Publication in refereed journal

C2 - 31476618

SN - 2589-0042

VL - 19

SP - 715

EP - 727

JO - iScience

JF - iScience

ER -

Pim1 Impacts Enterovirus A71 Replication and Represents a Potential Target in Antiviral Therapy

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GRF: The Molecular Mechanism of PIM1 Response to Facilitate Human Enterovirus 71 Infection

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Pim1 Impacts Enterovirus A71 Replication and Represents a Potential Target in Antiviral Therapy

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GRF: The Molecular Mechanism of PIM1 Response to Facilitate Human Enterovirus 71 Infection

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