Lack of XBP-1 impedes murine cytomegalovirus gene expression.
The unfolded protein response (UPR) is an endoplasmic reticulum (ER)-to-nucleus signaling cascade induced in response to ER stress. The UPR aims at restoring homeostasis, but can also induce apoptosis if stress persists. Infection by human and murine cytomegaloviruses (CMVs) provokes ER stress and i...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4205010?pdf=render |
| _version_ | 1818296435386351616 |
|---|---|
| author | Adi Drori Martin Messerle Wolfram Brune Boaz Tirosh |
| author_facet | Adi Drori Martin Messerle Wolfram Brune Boaz Tirosh |
| author_sort | Adi Drori |
| collection | DOAJ |
| description | The unfolded protein response (UPR) is an endoplasmic reticulum (ER)-to-nucleus signaling cascade induced in response to ER stress. The UPR aims at restoring homeostasis, but can also induce apoptosis if stress persists. Infection by human and murine cytomegaloviruses (CMVs) provokes ER stress and induces the UPR. However, both CMVs manipulate the UPR to promote its prosurvival activity and delay apoptosis. The underlying mechanisms remain largely unknown. Recently, we demonstrated that MCMV and HCMV encode a late protein to target IRE1 for degradation. However, the importance of its downstream effector, X Box binding protein 1 (XBP-1), has not been directly studied. Here we show that deletion of XBP-1 prior to or early after infection confers a transient delay in viral propagation in fibroblasts that can be overcome by increasing the viral dose. A similar phenotype was demonstrated in peritoneal macrophages. In vivo, acute infection by MCMV is reduced in the absence of XBP-1. Our data indicate that removal of XBP-1 confers a kinetic delay in early stages of MCMV infection and suggest that the late targeting of IRE1 is aimed at inhibiting activities other than the splicing of XBP-1 mRNA. |
| first_indexed | 2024-12-13T04:03:30Z |
| format | Article |
| id | doaj.art-cac23c12425c4f70acd768371b84eac9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T04:03:30Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-cac23c12425c4f70acd768371b84eac92022-12-22T00:00:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01910e11094210.1371/journal.pone.0110942Lack of XBP-1 impedes murine cytomegalovirus gene expression.Adi DroriMartin MesserleWolfram BruneBoaz TiroshThe unfolded protein response (UPR) is an endoplasmic reticulum (ER)-to-nucleus signaling cascade induced in response to ER stress. The UPR aims at restoring homeostasis, but can also induce apoptosis if stress persists. Infection by human and murine cytomegaloviruses (CMVs) provokes ER stress and induces the UPR. However, both CMVs manipulate the UPR to promote its prosurvival activity and delay apoptosis. The underlying mechanisms remain largely unknown. Recently, we demonstrated that MCMV and HCMV encode a late protein to target IRE1 for degradation. However, the importance of its downstream effector, X Box binding protein 1 (XBP-1), has not been directly studied. Here we show that deletion of XBP-1 prior to or early after infection confers a transient delay in viral propagation in fibroblasts that can be overcome by increasing the viral dose. A similar phenotype was demonstrated in peritoneal macrophages. In vivo, acute infection by MCMV is reduced in the absence of XBP-1. Our data indicate that removal of XBP-1 confers a kinetic delay in early stages of MCMV infection and suggest that the late targeting of IRE1 is aimed at inhibiting activities other than the splicing of XBP-1 mRNA.http://europepmc.org/articles/PMC4205010?pdf=render |
| spellingShingle | Adi Drori Martin Messerle Wolfram Brune Boaz Tirosh Lack of XBP-1 impedes murine cytomegalovirus gene expression. PLoS ONE |
| title | Lack of XBP-1 impedes murine cytomegalovirus gene expression. |
| title_full | Lack of XBP-1 impedes murine cytomegalovirus gene expression. |
| title_fullStr | Lack of XBP-1 impedes murine cytomegalovirus gene expression. |
| title_full_unstemmed | Lack of XBP-1 impedes murine cytomegalovirus gene expression. |
| title_short | Lack of XBP-1 impedes murine cytomegalovirus gene expression. |
| title_sort | lack of xbp 1 impedes murine cytomegalovirus gene expression |
| url | http://europepmc.org/articles/PMC4205010?pdf=render |
| work_keys_str_mv | AT adidrori lackofxbp1impedesmurinecytomegalovirusgeneexpression AT martinmesserle lackofxbp1impedesmurinecytomegalovirusgeneexpression AT wolframbrune lackofxbp1impedesmurinecytomegalovirusgeneexpression AT boaztirosh lackofxbp1impedesmurinecytomegalovirusgeneexpression |