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Scientific article
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English

The UPR sensor IRE1α and the adenovirus E3-19K glycoprotein sustain persistent and lytic infections

Contributors

Prasad, Vibhu; Suomalainen, Maarit; Jasiqi, Yllza; Hemmi, Silvio; Hearing, Patrick; Hosie, Louise; Burgert, Hans-Gerhard; Greber, Urs F

Published in

Nature communications, vol. 11, no. 1, 1997

Publication date

2020-04-24

First online date

2020-04-24

Abstract

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.

Keywords

  • A549 Cells
  • Adenoviridae / genetics
  • Adenoviridae / immunology
  • Adenoviridae / pathogenicity
  • Adenoviridae Infections / genetics
  • Adenoviridae Infections / immunology
  • Adenoviridae Infections / virology
  • Adenovirus E1A Proteins / genetics
  • Adenovirus E3 Proteins / metabolism
  • Chronic Disease
  • Endoplasmic Reticulum / metabolism
  • Endoribonucleases / genetics
  • Endoribonucleases / metabolism
  • Gene Expression Regulation, Viral / immunology
  • Gene Knockdown Techniques
  • Gene Knockout Techniques
  • HeLa Cells
  • Host-Pathogen Interactions / genetics
  • Humans
  • Immunocompromised Host
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • RNA Splicing
  • Virus Latency
  • Virus Release / genetics
  • X-Box Binding Protein 1 / genetics

UNIGE affiliation entities

Not a UNIGE publication

UNIGE research groups

Citation (ISO format)

PRASAD, Vibhu et al. The UPR sensor IRE1α and the adenovirus E3-19K glycoprotein sustain persistent and lytic infections. In: Nature communications, 2020, vol. 11, n° 1, p. 1997. doi: 10.1038/s41467-020-15844-2

Main files (1)

Article (Published version)
CC BY-4.0

Identifiers

Additional URL for this publication

https://www.nature.com/articles/s41467-020-15844-2

Journal ISSN

2041-1723
104views
49downloads

Technical informations

Creation

18/11/2024 13:48:55

First validation

20/11/2024 07:59:50

Update

20/11/2024 07:59:50

Status update

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Last indexation

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