ArticlePloS one2011
Hepatitis E virus ORF2 protein activates the pro-apoptotic gene CHOP and anti-apoptotic heat shock proteins.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 51 citations in OpenAlex.
- Hepatitis E virus genome plasticity: a marker of chronicity and therapy failure?Communications biology · 2026Review
- Associations of ambient temperature and heat waves with risks of hepatitis E in Jiangsu, China (2010-2023): A time-stratified case-crossover study.Infectious Disease Modelling · 2026Article
- GRP75 blocks hepatitis E virus infection by targeting HEV-ORF2 for degradation through chaperone-mediated autophagy and promoting IRF3 activation.Journal of virology · 2026Article
- Mitochondrial and lipid metabolism rewiring during HEV infection.Cellular and molecular life sciences : CMLS · 2026Article
- Orf132: a critical gene for LSDV replication and its role in Er stress-related apoptosis.Virology journal · 2025Article
- Glucose and glutamine drive hepatitis E virus replication.Archives of virology · 2024Article
- Viral Hepatitis: Host Immune Interaction, Pathogenesis and New Therapeutic Strategies.Pathogens (Basel, Switzerland) · 2024Review
- Genetic characterization, structural analysis, and detection of positive selection in small heat shock proteins of Cypriniformes and Clupeiformes.Fish physiology and biochemistry · 2024Article
- Immunobiology and Host Response to HEV.Advances in experimental medicine and biology · 2023Article
- Characteristics and Functions of HEV Proteins.Advances in experimental medicine and biology · 2023Article
- Structural aspects of hepatitis E virus.Archives of virology · 2022Review
- Review
- Beyond the Usual Suspects: Hepatitis E Virus and Its Implications in Hepatocellular Carcinoma.Cancers · 2021Review
- Cellular Organelles Involved in Hepatitis E Virus Infection.Pathogens (Basel, Switzerland) · 2021Review
- Hepatitis E Virus Immunopathogenesis.Pathogens (Basel, Switzerland) · 2021Review
- Interplay between Hepatitis E Virus and Host Cell Pattern Recognition Receptors.International journal of molecular sciences · 2021Review
- The Hepatitis E Virus Open Reading Frame 2 Protein: Beyond Viral Capsid.Frontiers in microbiology · 2021Review
- A Bioinformatic Analysis of Correlations between Polymeric Immunoglobulin Receptor (PIGR) and Liver Fibrosis Progression.BioMed research international · 2021Article
- Hepatitis E Virus: How It Escapes Host Innate Immunity.Vaccines · 2020Review
- Hepatitis E virus infection during pregnancy.Virology journal · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatitis E virus (HEV) is a non-enveloped plus-strand RNA virus that causes acute hepatitis. The capsid protein open reading frame 2 (ORF2) is known to induce endoplasmic reticulum stress in ORF2 expressing cells. METHODOLOGY/PRINCIPAL
findingsIn this study we found that HEV ORF2 activates the expression of the pro-apoptotic gene C/EBP homologous protein (CHOP). ORF2 stimulates the CHOP promoter mainly through AARE (amino acid response elements) and to a minor extent the ERSE (endoplasmic reticulum stress response elements). Activating transcription factor 4 (ATF4) protein binds and activates the AARE regulatory sites of the CHOP promoter. ORF2 expression also leads to increased phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) that in turn initiates the translation of ATF4 mRNA. The pro-apoptotic gene CHOP is an important trigger to initiate endoplasmic reticulum stress induced apoptosis. However, the activation of CHOP by ORF2 in this study did not induce apoptosis, nor did BCL2-associated X protein (Bax) translocate to mitochondria. Microarray analysis revealed an ORF2 specific increased expression of chaperones Hsp72, Hsp70B', and co-chaperone Hsp40. Co-immunoprecipitation (Co-IP) and in silico molecular docking analysis suggests that HEV ORF2 interacts with Hsp72. In addition, Hsp72 shows nuclear accumulation in ORF2 expressing cells. CONCLUSIONS/SIGNIFICANCE: These data provide new insight into simultaneously occurring counter-acting effects of HEV ORF2 that may be part of a strategy to prevent host suicide before completion of the viral replication cycle.
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