EV71 3C protease induces apoptosis by cleavage of hnRNP A1 to promote apaf-1 translation.

Enterovirus 71 (EV71) induces apoptosis to promote viral particle release. Earlier work showed that EV71 utilizes its 3C protease to induce apoptosis in a caspase-3-dependent pathway, though the mechanism is unknown. However, work from Vagner, Holcik and colleagues showed that host protein heterogen...

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Main Authors: Mei-Ling Li, Jing-Yi Lin, Bo-Shiun Chen, Kuo-Feng Weng, Shin-Ru Shih, Jesse Davila Calderon, Blanton S Tolbert, Gary Brewer
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0221048
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spelling doaj-28d0401486314236bb1ca9c517ed92a72021-03-04T11:21:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01149e022104810.1371/journal.pone.0221048EV71 3C protease induces apoptosis by cleavage of hnRNP A1 to promote apaf-1 translation.Mei-Ling LiJing-Yi LinBo-Shiun ChenKuo-Feng WengShin-Ru ShihJesse Davila CalderonBlanton S TolbertGary BrewerEnterovirus 71 (EV71) induces apoptosis to promote viral particle release. Earlier work showed that EV71 utilizes its 3C protease to induce apoptosis in a caspase-3-dependent pathway, though the mechanism is unknown. However, work from Vagner, Holcik and colleagues showed that host protein heterogeneous ribonucleoprotein A1 (hnRNP A1) binds the IRES of cellular apoptotic peptidase activating factor 1 (apaf-1) mRNA to repress its translation. In this work, we show that apaf-1 expression is essential for EV71-induced apoptosis. EV71 infection or ectopic expression of 3C protease cleaves hnRNP A1, which abolishes its binding to the apaf-1 IRES. This allows IRES-dependent synthesis of apaf-1, activation of caspase-3, and apoptosis. Thus, we reveal a novel mechanism that EV71 utilizes for virus release via a 3C protease-hnRNP A1-apaf-1-caspase-3-apoptosis axis.https://doi.org/10.1371/journal.pone.0221048
collection DOAJ
language English
format Article
sources DOAJ
author Mei-Ling Li
Jing-Yi Lin
Bo-Shiun Chen
Kuo-Feng Weng
Shin-Ru Shih
Jesse Davila Calderon
Blanton S Tolbert
Gary Brewer
spellingShingle Mei-Ling Li
Jing-Yi Lin
Bo-Shiun Chen
Kuo-Feng Weng
Shin-Ru Shih
Jesse Davila Calderon
Blanton S Tolbert
Gary Brewer
EV71 3C protease induces apoptosis by cleavage of hnRNP A1 to promote apaf-1 translation.
PLoS ONE
author_facet Mei-Ling Li
Jing-Yi Lin
Bo-Shiun Chen
Kuo-Feng Weng
Shin-Ru Shih
Jesse Davila Calderon
Blanton S Tolbert
Gary Brewer
author_sort Mei-Ling Li
title EV71 3C protease induces apoptosis by cleavage of hnRNP A1 to promote apaf-1 translation.
title_short EV71 3C protease induces apoptosis by cleavage of hnRNP A1 to promote apaf-1 translation.
title_full EV71 3C protease induces apoptosis by cleavage of hnRNP A1 to promote apaf-1 translation.
title_fullStr EV71 3C protease induces apoptosis by cleavage of hnRNP A1 to promote apaf-1 translation.
title_full_unstemmed EV71 3C protease induces apoptosis by cleavage of hnRNP A1 to promote apaf-1 translation.
title_sort ev71 3c protease induces apoptosis by cleavage of hnrnp a1 to promote apaf-1 translation.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2019-01-01
description Enterovirus 71 (EV71) induces apoptosis to promote viral particle release. Earlier work showed that EV71 utilizes its 3C protease to induce apoptosis in a caspase-3-dependent pathway, though the mechanism is unknown. However, work from Vagner, Holcik and colleagues showed that host protein heterogeneous ribonucleoprotein A1 (hnRNP A1) binds the IRES of cellular apoptotic peptidase activating factor 1 (apaf-1) mRNA to repress its translation. In this work, we show that apaf-1 expression is essential for EV71-induced apoptosis. EV71 infection or ectopic expression of 3C protease cleaves hnRNP A1, which abolishes its binding to the apaf-1 IRES. This allows IRES-dependent synthesis of apaf-1, activation of caspase-3, and apoptosis. Thus, we reveal a novel mechanism that EV71 utilizes for virus release via a 3C protease-hnRNP A1-apaf-1-caspase-3-apoptosis axis.
url https://doi.org/10.1371/journal.pone.0221048
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