scholarly journals Amino acid substitutions in the non-structural proteins 4A or 4B modulate the induction of autophagy in West Nile virus infected cells independently of the activation of the unfolded protein response

2015 ◽  
Vol 5 ◽  
Author(s):  
Ana-Belén Blázquez ◽  
Miguel A. Martín-Acebes ◽  
Juan-Carlos Saiz
Keyword(s):  
West Nile Virus ◽  
Amino Acid ◽  
Unfolded Protein Response ◽  
Structural Proteins ◽  
Amino Acid Substitutions ◽  
West Nile ◽  
Unfolded Protein ◽  
Infected Cells ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals West Nile Virus Infection Activates the Unfolded Protein Response, Leading to CHOP Induction and Apoptosis

2007 ◽  
Vol 81 (20) ◽  
pp. 10849-10860 ◽  
Author(s):  
Guruprasad R. Medigeshi ◽  
Alissa M. Lancaster ◽  
Alec J. Hirsch ◽  
Thomas Briese ◽  
W. Ian Lipkin ◽  
...  
Keyword(s):  
Transcription Factor ◽  
West Nile Virus ◽  
Unfolded Protein Response ◽  
Neuronal Damage ◽  
Initiation Factor ◽  
West Nile ◽  
Human Neuroblastoma ◽  
Unfolded Protein ◽  
Infected Cells ◽  
Protein Response

ABSTRACT West Nile virus (WNV)-mediated neuronal death is a hallmark of WNV meningitis and encephalitis. However, the mechanisms of WNV-induced neuronal damage are not well understood. We investigated WNV neuropathogenesis by using human neuroblastoma cells and primary rat hippocampal neurons. We observed that WNV activates multiple unfolded protein response (UPR) pathways, leading to transcriptional and translational induction of UPR target genes. We evaluated the role of the three major UPR pathways, namely, inositol-requiring enzyme 1-dependent splicing of X box binding protein 1 (XBP1) mRNA, activation of activating transcription factor 6 (ATF6), and protein kinase R-like endoplasmic reticulum (ER) kinase-dependent eukaryotic initiation factor 2α (eIF2α) phosphorylation, in WNV-infected cells. We show that XBP1 is nonessential or can be replaced by other UPR pathways in WNV replication. ATF6 was rapidly degraded by proteasomes, consistent with induction of ER stress by WNV. We further observed a transient phosphorylation of eIF2α and induction of the proapoptotic cyclic AMP response element-binding transcription factor homologous protein (CHOP). WNV-infected cells exhibited a number of apoptotic phenotypes, such as (i) induction of growth arrest and DNA damage-inducible gene 34, (ii) activation of caspase-3, and (iii) cleavage of poly(ADP-ribose) polymerase. The expression of WNV nonstructural proteins alone was sufficient to induce CHOP expression. Importantly, WNV grew to significantly higher viral titers in chop − / − mouse embryonic fibroblasts (MEFs) than in wild-type MEFs, suggesting that CHOP-dependent premature cell death represents a host defense mechanism to limit viral replication that might also be responsible for the widespread neuronal loss observed in WNV-infected neuronal tissue.

Intestinal Amino Acid Availability via PEPT-1 Affects TORC1/2 Signaling and the Unfolded Protein Response

2014 ◽  
Vol 13 (8) ◽  
pp. 3685-3692 ◽  
Author(s):  
Kerstin E. Geillinger ◽  
Katja Kuhlmann ◽  
Martin Eisenacher ◽  
Pieter Giesbertz ◽  
Helmut E. Meyer ◽  
...  
Keyword(s):  
Amino Acid ◽  
Unfolded Protein Response ◽  
Unfolded Protein ◽  
Amino Acid Availability ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals Manipulation of the unfolded protein response: A pharmacological strategy against coronavirus infection

2021 ◽  
Vol 17 (6) ◽  
pp. e1009644
Author(s):  
Liliana Echavarría-Consuegra ◽  
Georgia M. Cook ◽  
Idoia Busnadiego ◽  
Charlotte Lefèvre ◽  
Sarah Keep ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Hepatitis Virus ◽  
Ribosome Profiling ◽  
Murine Hepatitis Virus ◽  
Unfolded Protein ◽  
Virion Release ◽  
Infected Cells ◽  
Coronavirus Infection ◽  
The Unfolded Protein Response ◽  
Protein Response

Coronavirus infection induces the unfolded protein response (UPR), a cellular signalling pathway composed of three branches, triggered by unfolded proteins in the endoplasmic reticulum (ER) due to high ER load. We have used RNA sequencing and ribosome profiling to investigate holistically the transcriptional and translational response to cellular infection by murine hepatitis virus (MHV), often used as a model for the Betacoronavirus genus to which the recently emerged SARS-CoV-2 also belongs. We found the UPR to be amongst the most significantly up-regulated pathways in response to MHV infection. To confirm and extend these observations, we show experimentally the induction of all three branches of the UPR in both MHV- and SARS-CoV-2-infected cells. Over-expression of the SARS-CoV-2 ORF8 or S proteins alone is itself sufficient to induce the UPR. Remarkably, pharmacological inhibition of the UPR greatly reduced the replication of both MHV and SARS-CoV-2, revealing the importance of this pathway for successful coronavirus replication. This was particularly striking when both IRE1α and ATF6 branches of the UPR were inhibited, reducing SARS-CoV-2 virion release (~1,000-fold). Together, these data highlight the UPR as a promising antiviral target to combat coronavirus infection.

scholarly journals Amino acid limitation regulates CHOP expression through a specific pathway independent of the unfolded protein response

FEBS Letters ◽  
1999 ◽  
Vol 448 (2-3) ◽  
pp. 211-216 ◽  
Author(s):  
Céline Jousse ◽  
Alain Bruhat ◽  
Heather P Harding ◽  
Marc Ferrara ◽  
David Ron ◽  
...  
Keyword(s):  
Amino Acid ◽  
Unfolded Protein Response ◽  
Unfolded Protein ◽  
Chop Expression ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Specific Pathway

Oestrogen-driven changes in the bovine uterus are associated with activation of the unfolded protein response

2014 ◽  
Author(s):  
Mohammed A Alfattah ◽  
Paul Anthony McGettigan ◽  
John Arthur Browne ◽  
Khalid M Alkhodair ◽  
Katarzyna Pluta ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response
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