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Since HEV was identified as a zoonotic pathogen, different species of HEV strains have been globally identified from various hosts, leading to an expanding range of hosts. The HEV genome consists of a 5' noncoding region, three open reading frames (ORFs), and a 3' noncoding region. The ORF3 protein is the smallest but has many functions in HEV release and pathogenesis. In this review, we systematically summarize recent progress in understanding the functions of the HEV ORF3 protein in virion release, biogenesis of quasi\u2010enveloped viruses, antigenicity, and host environmental regulation. This review will help us to understand HEV replication and pathogenesis mechanisms better.<\/jats:p>","DOI":"10.1002\/jmv.29691","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T03:13:57Z","timestamp":1716520437000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Multifunctional ORF3 protein of hepatitis E virus"],"prefix":"10.1002","volume":"96","author":[{"given":"Xiaoxuan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Veterinary Medicine Northwest Agriculture and Forestry University, Yangling  Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuwen","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Veterinary Medicine Northwest Agriculture and Forestry University, Yangling  Shaanxi 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