BPIFB3 Regulates Autophagy and Coxsackievirus B Replication through a Noncanonical Pathway Independent of the Core Initiation Machinery

BPIFB3 Regulates Autophagy and Coxsackievirus B Replication through a Noncanonical Pathway Independent of the Core Initiation Machinery

Enteroviruses require autophagy to facilitate the formation of autophagosome (AP)-like double-membrane vesicles that provide the scaffolding for RNA replication. Here, we identify bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 3 (BPIFB3) as a gene whose silencing...

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Main Authors: Delorme-Axford, Elizabeth, Morosky, Stefanie, Bomberger, Jennifer, Stolz, Donna B., Jackson, William T., Coyne, Carolyn B.
Format: Online
Language:English
Published: American Society of Microbiology 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324245/
id pubmed-4324245
recordtype oai_dc
spelling pubmed-43242452015-03-03 BPIFB3 Regulates Autophagy and Coxsackievirus B Replication through a Noncanonical Pathway Independent of the Core Initiation Machinery Delorme-Axford, Elizabeth Morosky, Stefanie Bomberger, Jennifer Stolz, Donna B. Jackson, William T. Coyne, Carolyn B. Research Article Enteroviruses require autophagy to facilitate the formation of autophagosome (AP)-like double-membrane vesicles that provide the scaffolding for RNA replication. Here, we identify bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 3 (BPIFB3) as a gene whose silencing greatly enhances coxsackievirus B (CVB) replication and induces dramatic alterations in the morphology of CVB-induced replication organelles. We show that BPIFB3 is associated with the endoplasmic reticulum (ER), and its silencing by RNA interference enhances basal levels of autophagy and promotes increased autophagy during CVB replication. Conversely, overexpression of BPIFB3 inhibits CVB replication, dramatically alters the morphology of LC3B-positive vesicles, and suppresses autophagy in response to rapamaycin. In addition, we found that, whereas silencing of core autophagy components associated with the initiation of APs in control cells suppressed CVB replication, silencing of these same components had no effect on CVB-induced autophagy or viral replication in cells transfected with BPIFB3 small interfering RNA. Based on these results, taken together, this study reports on a previously uncharacterized regulator of enterovirus infection that controls replication through a noncanonical pathway independent from the core autophagy initiation machinery. American Society of Microbiology 2014-12-09 /pmc/articles/PMC4324245/ /pubmed/25491355 http://dx.doi.org/10.1128/mBio.02147-14 Text en Copyright © 2014 Delorme-Axford et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Delorme-Axford, Elizabeth
Morosky, Stefanie
Bomberger, Jennifer
Stolz, Donna B.
Jackson, William T.
Coyne, Carolyn B.
spellingShingle Delorme-Axford, Elizabeth
Morosky, Stefanie
Bomberger, Jennifer
Stolz, Donna B.
Jackson, William T.
Coyne, Carolyn B.
BPIFB3 Regulates Autophagy and Coxsackievirus B Replication through a Noncanonical Pathway Independent of the Core Initiation Machinery
author_facet Delorme-Axford, Elizabeth
Morosky, Stefanie
Bomberger, Jennifer
Stolz, Donna B.
Jackson, William T.
Coyne, Carolyn B.
author_sort Delorme-Axford, Elizabeth
title BPIFB3 Regulates Autophagy and Coxsackievirus B Replication through a Noncanonical Pathway Independent of the Core Initiation Machinery
title_short BPIFB3 Regulates Autophagy and Coxsackievirus B Replication through a Noncanonical Pathway Independent of the Core Initiation Machinery
title_full BPIFB3 Regulates Autophagy and Coxsackievirus B Replication through a Noncanonical Pathway Independent of the Core Initiation Machinery
title_fullStr BPIFB3 Regulates Autophagy and Coxsackievirus B Replication through a Noncanonical Pathway Independent of the Core Initiation Machinery
title_full_unstemmed BPIFB3 Regulates Autophagy and Coxsackievirus B Replication through a Noncanonical Pathway Independent of the Core Initiation Machinery
title_sort bpifb3 regulates autophagy and coxsackievirus b replication through a noncanonical pathway independent of the core initiation machinery
description Enteroviruses require autophagy to facilitate the formation of autophagosome (AP)-like double-membrane vesicles that provide the scaffolding for RNA replication. Here, we identify bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 3 (BPIFB3) as a gene whose silencing greatly enhances coxsackievirus B (CVB) replication and induces dramatic alterations in the morphology of CVB-induced replication organelles. We show that BPIFB3 is associated with the endoplasmic reticulum (ER), and its silencing by RNA interference enhances basal levels of autophagy and promotes increased autophagy during CVB replication. Conversely, overexpression of BPIFB3 inhibits CVB replication, dramatically alters the morphology of LC3B-positive vesicles, and suppresses autophagy in response to rapamaycin. In addition, we found that, whereas silencing of core autophagy components associated with the initiation of APs in control cells suppressed CVB replication, silencing of these same components had no effect on CVB-induced autophagy or viral replication in cells transfected with BPIFB3 small interfering RNA. Based on these results, taken together, this study reports on a previously uncharacterized regulator of enterovirus infection that controls replication through a noncanonical pathway independent from the core autophagy initiation machinery.
publisher American Society of Microbiology
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324245/
_version_ 1613186733887717376

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