The UPR sensor IRE1α and the adenovirus E3-19K glycoprotein sustain persistent and lytic infections.
A549 Cells
Adenoviridae
/ genetics
Adenoviridae Infections
/ genetics
Adenovirus E1A Proteins
/ genetics
Adenovirus E3 Proteins
/ metabolism
Chronic Disease
Endoplasmic Reticulum
/ metabolism
Endoribonucleases
/ genetics
Gene Expression Regulation, Viral
/ immunology
Gene Knockdown Techniques
Gene Knockout Techniques
HeLa Cells
Host-Pathogen Interactions
/ genetics
Humans
Immunocompromised Host
Interferon-gamma
/ genetics
Protein Serine-Threonine Kinases
/ genetics
RNA Splicing
Virus Latency
Virus Release
/ genetics
X-Box Binding Protein 1
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 04 2020
24 04 2020
Historique:
received:
14
01
2020
accepted:
30
03
2020
entrez:
26
4
2020
pubmed:
26
4
2020
medline:
11
8
2020
Statut:
epublish
Résumé
Persistent viruses cause chronic disease, and threaten the lives of immunosuppressed individuals. Here, we elucidate a mechanism supporting the persistence of human adenovirus (AdV), a virus that can kill immunosuppressed patients. Cell biological analyses, genetics and chemical interference demonstrate that one of five AdV membrane proteins, the E3-19K glycoprotein specifically triggers the unfolded protein response (UPR) sensor IRE1α in the endoplasmic reticulum (ER), but not other UPR sensors, such as protein kinase R-like ER kinase (PERK) and activating transcription factor 6 (ATF6). The E3-19K lumenal domain activates the IRE1α nuclease, which initiates mRNA splicing of X-box binding protein-1 (XBP1). XBP1s binds to the viral E1A-enhancer/promoter sequence, and boosts E1A transcription, E3-19K levels and lytic infection. Inhibition of IRE1α nuclease interrupts the five components feedforward loop, E1A, E3-19K, IRE1α, XBP1s, E1A enhancer/promoter. This loop sustains persistent infection in the presence of the immune activator interferon, and lytic infection in the absence of interferon.
Identifiants
pubmed: 32332742
doi: 10.1038/s41467-020-15844-2
pii: 10.1038/s41467-020-15844-2
pmc: PMC7181865
doi:
Substances chimiques
Adenovirus E1A Proteins
0
Adenovirus E3 Proteins
0
IFNG protein, human
0
X-Box Binding Protein 1
0
XBP1 protein, human
0
Interferon-gamma
82115-62-6
ERN1 protein, human
EC 2.7.11.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
Endoribonucleases
EC 3.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1997Subventions
Organisme : NCI NIH HHS
ID : R01 CA122677
Pays : United States
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