Inositol-requiring enzyme 1 inhibits respiratory syncytial virus replication

Ihab Hassan; Kayla S Gaines; Wesley J Hottel; Ryan M Wishy; Sara E Miller; Linda S Powers; D Thomas Rutkowski; Martha M Monick

doi:10.1074/jbc.M113.510594

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Inositol-requiring enzyme 1 inhibits respiratory syncytial virus replication

Journal article

Open access

Peer reviewed

Inositol-requiring enzyme 1 inhibits respiratory syncytial virus replication

Ihab Hassan, Kayla S Gaines, Wesley J Hottel, Ryan M Wishy, Sara E Miller, Linda S Powers, D Thomas Rutkowski and Martha M Monick

The Journal of biological chemistry, Vol.289(11), pp.7537-7546

03/14/2014

DOI: 10.1074/jbc.M113.510594

PMCID: PMC3953267

PMID: 24497642

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Abstract

Despite being a major health problem, respiratory syncytial virus (RSV) infections remain without specific therapy. Identification of novel host cellular responses that play a role in the pathogenesis of RSV infection is needed for therapeutic development. The endoplasmic reticulum (ER) stress response is an evolutionarily conserved cellular signaling cascade that has been implicated in multiple biological phenomena, including the pathogenesis of some viral infections. In this study, we investigate the role of the ER stress response in RSV infection using an in vitro A549 cell culture model. We found that RSV infection induces a non-canonical ER stress response with preferential activation of the inositol-requiring enzyme 1 (IRE1) and activated transcription factor 6 (ATF6) pathways with no concomitant significant activation of the protein kinase R-like ER kinase (PERK) pathway. Furthermore, we discovered that IRE1 has an inhibitory effect on RSV replication. Our data characterize, for the first time, the nature of the ER stress response in the setting of RSV infection and identify the IRE1 stress pathway as a novel cellular anti-RSV defense mechanism.

Signal Transduction

Endoribonucleases - metabolism

Respiratory Syncytial Viruses - physiology

Humans

Endoplasmic Reticulum - metabolism

Respiratory Syncytial Virus Infections - metabolism

Host-Pathogen Interactions

Activating Transcription Factor 6 - metabolism

RNA Splicing

Animals

Virus Replication

Gene Expression Regulation, Viral

Endoplasmic Reticulum Stress

Cell Line, Tumor

Mice

Protein-Serine-Threonine Kinases - metabolism

Fibroblasts - metabolism

Details

Title: Subtitle: Inositol-requiring enzyme 1 inhibits respiratory syncytial virus replication
Creators: Ihab Hassan - From the Department of Internal Medicine, Carver College of Medicine and
Kayla S Gaines
Wesley J Hottel
Ryan M Wishy
Sara E Miller
Linda S Powers
D Thomas Rutkowski
Martha M Monick
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.289(11), pp.7537-7546
DOI: 10.1074/jbc.M113.510594
PMID: 24497642
PMCID: PMC3953267
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Grant note: P30 ES005605 / NIEHS NIH HHS UL1RR024979 / NCRR NIH HHS R21 HL109589 / NHLBI NIH HHS R01 DK084058 / NIDDK NIH HHS R01 HL079901 / NHLBI NIH HHS R01 HL096625 / NHLBI NIH HHS UL1 RR024979 / NCRR NIH HHS
Language: English
Date published: 03/14/2014
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Anatomy and Cell Biology; Hygienic Laboratory - Bdc; Internal Medicine
Record Identifier: 9984094536102771

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