{
  "abstract": "Hepatitis E virus (HEV) is a major cause of acute viral hepatitis, with an estimated 20 million human infections annually. Its diverse host range presents a significant zoonotic threat, yet the molecular mechanisms underpinning HEV-host interactions remain poorly characterised. Here, we used transposon-based insertion screening of the HEV pORF1 polyprotein to identify a novel region within the viral PCP domain that permits HA-epitope insertion, enabling the first epitope tagging of this domain. Combined with V5 tagging of the hypervariable region (HVR), this approach enabled the generation of a replication-competent stable cell line expressing dual-tagged ORF1. Co-immunoprecipitation and TMT-based LC-MS proteomics revealed that pORF1 interacts with host proteins involved in endoplasmic reticulum-associated degradation (ERAD) and the 26S proteasome. Pharmacological inhibition demonstrated that both pathways are required for efficient HEV replication. Treatment with the FDA-approved proteasome inhibitor bortezomib altered pORF1 precursor abundance and led to loss of full-length pORF1 through enhanced proteolysis. Importantly, the kinetics of ORF1 degradation following proteasome inhibition correlated with immediate loss of HEV replication, demonstrating a functional link between pORF1 proteostasis and viral replication. Collectively, our findings identify the ERAD network as a previously unrecognised requirement for HEV replication and establish a role for the 26S proteasome in maintaining pORF1 proteostasis.",
  "abstract_shown": true,
  "affiliations": [
    "University of Leeds"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "K. M. Abualsaoud"
    },
    {
      "name": "F. J. Buchanan"
    },
    {
      "name": "O. M. Byford"
    },
    {
      "name": "E. M. Bartholomew"
    },
    {
      "name": "C. E. Williams"
    },
    {
      "name": "M. Kailani"
    },
    {
      "name": "R. Penrice-Randal"
    },
    {
      "name": "M. Harris"
    },
    {
      "affs": [
        0
      ],
      "name": "M. R. Herod"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f4z1fzgw1chjn.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.08.757567",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757567v1.full",
  "id": "f4z1fzgw1chjn",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757567v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "microbiology"
    ],
    [
      "openalex",
      "2721|Hepatitis Viruses Studies and Epidemiology"
    ]
  ],
  "openalex": "W7221331626",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757567v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-08",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/f4z1fzgw1chjn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:54Z",
      "native_id": "10.64898/2026.10.08.757567",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757567v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "The proteasome and ERAD pathways can regulate hepatitis E virus pORF1 proteostasis and genome replication",
  "title_text": "The proteasome and ERAD pathways can regulate hepatitis E virus pORF1 proteostasis and genome replication",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:54Z",
  "url": "https://research.draconitic.com/paper/f4z1fzgw1chjn",
  "venue": "bioRxiv",
  "versions": []
}