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Volume 104, Issue 2

Modulation of cellular autophagy by genotype 1 hepatitis E virus ORF3 protein No Access

Abstract

Hepatitis E virus (HEV) egresses from infected hepatocytes as quasienveloped particles containing open reading frame 3 (ORF3) protein. HEV ORF3 (small phosphoprotein) interacts with host proteins to establish a favourable environment for virus replication. It is a functional viroporin that plays an important role during virus release. Our study provides evidence that pORF3 plays a pivotal role in inducing Beclin1-mediated autophagy that helps HEV-1 replication as well as its exit from cells. The ORF3 interacts with host proteins involved in regulation of transcriptional activity, immune response, cellular and molecular processes, and modulation of autophagy, by interacting with proteins, DAPK1, ATG2B, ATG16L2 and also several histone deacetylases (HDACs). For autophagy induction, the ORF3 utilizes non-canonical NF-κB2 pathway and sequesters p52NF-κB and HDAC2 to upregulate DAPK1 expression, leading to enhanced Beclin1 phosphorylation. By sequestering several HDACs, HEV may prevent histone deacetylation to maintain overall cellular transcription intact to promote cell survival. Our findings highlight a novel crosstalk between cell survival pathways participating in ORF3-mediated autophagy

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): ATG7 , autophagy , Beclin1 , DAPK1 and HEV ORF3
Funding
This study was supported by the:
  • Department of Science and Technology (Award LS/358/2017)
    • Principle Award Recipient: ManjitaSrivastava
© 2023 ICMR-National Institute of Virology
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/content/journal/jgv/10.1099/jgv.0.001824
2023-02-21
2024-05-18
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Modulation of cellular autophagy by genotype 1 hepatitis E virus ORF3 protein
J. Gen. Virol. 104, 001824 (2023); https://doi.org/10.1099/jgv.0.001824
/content/journal/jgv/10.1099/jgv.0.001824
/content/journal/jgv/10.1099/jgv.0.001824
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