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Enteroviruses Manipulate the Unfolded Protein Response through Multifaceted Deregulation of the Ire1-Xbp1 Pathway.
- Source :
-
Viruses [Viruses] 2022 Nov 10; Vol. 14 (11). Date of Electronic Publication: 2022 Nov 10. - Publication Year :
- 2022
-
Abstract
- Many viruses are known to trigger endoplasmic reticulum (ER) stress in host cells, which in turn can develop a protective unfolded protein response (UPR). Depending on the conditions, the UPR may lead to either cell survival or programmed cell death. One of three UPR branches involves the upregulation of Xbp1 transcription factor caused by the unconventional cytoplasmic splicing of its mRNA. This process is accomplished by the phosphorylated form of the endoribonuclease/protein kinase Ire1/ERN1. Here, we show that the phosphorylation of Ire1 is up-regulated in HeLa cells early in enterovirus infection but down-regulated at later stages. We also find that Ire1 is cleaved in poliovirus- and coxsackievirus-infected HeLa cells 4-6 h after infection. We further show that the Ire1-mediated Xbp1 mRNA splicing is repressed in infected cells in a time-dependent manner. Thus, our results demonstrate the ability of enteroviruses to actively modulate the Ire1-Xbp1 host defensive pathway by inducing phosphorylation and proteolytic cleavage of the ER stress sensor Ire1, as well as down-regulating its splicing activity. Inactivation of Ire1 could be a novel mode of the UPR manipulation employed by viruses to modify the ER stress response in the infected cells.
- Subjects :
- Humans
Endoplasmic Reticulum Stress
Endoribonucleases genetics
Endoribonucleases metabolism
HeLa Cells
Protein Serine-Threonine Kinases genetics
RNA, Messenger genetics
Signal Transduction
Unfolded Protein Response
X-Box Binding Protein 1 genetics
X-Box Binding Protein 1 metabolism
Enterovirus genetics
Enterovirus Infections
Subjects
Details
- Language :
- English
- ISSN :
- 1999-4915
- Volume :
- 14
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Viruses
- Publication Type :
- Academic Journal
- Accession number :
- 36366584
- Full Text :
- https://doi.org/10.3390/v14112486