Hepatovirus translation requires PDGFA-associated protein 1, an eIF4E-binding protein regulating endoplasmic reticulum stress responses

The overexpression and misfolding of viral proteins in the endoplasmic reticulum (ER) may cause cellular stress, thereby inducing a cytoprotective, proteostatic host response involving phosphorylation of eukaryotic translation initiation factor 2 subunit alpha (eIF2α). Here, we show that hepatitis A virus, a positive-strand RNA virus responsible for infectious hepatitis, adopts a stress-resistant, eIF2α-independent mechanism of translation to ensure the synthesis of viral proteins within the infected liver. Cap-independent translation directed by the hepatovirus internal ribosome entry site and productive hepatovirus infection of mice both require platelet-derived growth factor subunit A (PDGFA)-associated protein 1 (PDAP1), a small phosphoprotein of unknown function with eIF4E-binding activity. PDAP1 also interacts with eIF1A and is essential for translating stress-resistant host messenger RNAs that evade the proteostatic response to ER stress and that encode proteins promoting the survival of stressed cells.

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Publication Details

Journal
UNC Libraries
Published
2024-12-04
DOI
https://doi.org/10.17615/yqb1-f602
Primary Topic
Endoplasmic Reticulum Stress and Disease
Type
article
Field-Weighted Citation Impact
0.00

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article

Hepatovirus translation requires PDGFA-associated protein 1, an eIF4E-binding protein regulating endoplasmic reticulum stress responses

John Michael Cullen, Erik M. Lenarcic, Craig E. Cameron, Stanley M. Lemon et al.
UNC Libraries
Endoplasmic Reticulum Stress and Disease
article

Hepatovirus translation requires PDGFA-associated protein 1, an eIF4E-binding protein regulating endoplasmic reticulum stress responses

John Michael Cullen, Erik M. Lenarcic, Craig E. Cameron, Stanley M. Lemon, Joseph A. Duncan, Hyejeong Kim, Takayoshi Shirasaki, Mélissa Léger-Abraham, Nathaniel J. Moorman, Bryan Yonish, Xian Chen, Ichiro Misumi, Jason K. Whitmire, You Li, Ling Xie, Anshuman Das, William G. Fusco
article en

Abstract

The overexpression and misfolding of viral proteins in the endoplasmic reticulum (ER) may cause cellular stress, thereby inducing a cytoprotective, proteostatic host response involving phosphorylation of eukaryotic translation initiation factor 2 subunit alpha (eIF2α). Here, we show that hepatitis A virus, a positive-strand RNA virus responsible for infectious hepatitis, adopts a stress-resistant, eIF2α-independent mechanism of translation to ensure the synthesis of viral proteins within the infected liver. Cap-independent translation directed by the hepatovirus internal ribosome entry site and productive hepatovirus infection of mice both require platelet-derived growth factor subunit A (PDGFA)-associated protein 1 (PDAP1), a small phosphoprotein of unknown function with eIF4E-binding activity. PDAP1 also interacts with eIF1A and is essential for translating stress-resistant host messenger RNAs that evade the proteostatic response to ER stress and that encode proteins promoting the survival of stressed cells.

UNC Libraries
University of North Carolina at Chapel Hill (US)
National Institutes of Health, University of North Carolina at Chapel Hill, National Cancer Institute, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
Openalex Percentile: Top 77%
Endoplasmic Reticulum Stress and Disease
DOIOpen Access PDFOpenAlex
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