Nele Gremmel, Mirco Glitscher, Johannes Scholz, Ashish Gadicherla, Reimar Johne, Eberhard Hildt, Paul Becher
{"title":"准包膜戊型肝炎病毒的细胞系依赖性释放揭示了在缺乏pORF3的情况下高尔基蛋白相关的另一种输出。","authors":"Nele Gremmel, Mirco Glitscher, Johannes Scholz, Ashish Gadicherla, Reimar Johne, Eberhard Hildt, Paul Becher","doi":"10.3389/fcimb.2025.1661270","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Hepatitis E virus (HEV) particles are released from infected cells in a quasi-enveloped form, typically via the multivesicular body (MVB) pathway, which is mediated by the viral accessory protein pORF3. However, cell-type specific aspects of this release mechanism remain poorly understood.</p><p><strong>Methods: </strong>We analyzed the release and envelopment characteristics of a pORF3-deficient genotype 3c HEV (HEVΔORF3) in comparison to wild-type HEV (HEVwt) in two human cell lines: hepatoma-derived PLC/PRF/5 and lung carcinoma-derived A549/D3 cells.</p><p><strong>Results: </strong>While viral release of HEVΔORF3 was strongly impaired in A549/D3 cells, PLC/PRF/5 cells supported efficient viral release despite the absence of pORF3. In PLC/PRF/5 cells, HEV particles retained quasi-envelopment and utilized an alternative, Golgi-associated egress pathway in the absence of pORF3. In contrast, A549/D3 cells did not support this compensatory release route.</p><p><strong>Conclusion: </strong>Our findings highlight a pronounced cell line-dependent variability in HEV release pathways, emphasizing the importance of cellular context in studies of HEV biology and antiviral strategies targeting virus egress.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1661270"},"PeriodicalIF":4.8000,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446258/pdf/","citationCount":"0","resultStr":"{\"title\":\"Cell line-dependent release of quasi-enveloped hepatitis E virus reveals alternative Golgi-associated egress in the absence of pORF3.\",\"authors\":\"Nele Gremmel, Mirco Glitscher, Johannes Scholz, Ashish Gadicherla, Reimar Johne, Eberhard Hildt, Paul Becher\",\"doi\":\"10.3389/fcimb.2025.1661270\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Hepatitis E virus (HEV) particles are released from infected cells in a quasi-enveloped form, typically via the multivesicular body (MVB) pathway, which is mediated by the viral accessory protein pORF3. However, cell-type specific aspects of this release mechanism remain poorly understood.</p><p><strong>Methods: </strong>We analyzed the release and envelopment characteristics of a pORF3-deficient genotype 3c HEV (HEVΔORF3) in comparison to wild-type HEV (HEVwt) in two human cell lines: hepatoma-derived PLC/PRF/5 and lung carcinoma-derived A549/D3 cells.</p><p><strong>Results: </strong>While viral release of HEVΔORF3 was strongly impaired in A549/D3 cells, PLC/PRF/5 cells supported efficient viral release despite the absence of pORF3. In PLC/PRF/5 cells, HEV particles retained quasi-envelopment and utilized an alternative, Golgi-associated egress pathway in the absence of pORF3. In contrast, A549/D3 cells did not support this compensatory release route.</p><p><strong>Conclusion: </strong>Our findings highlight a pronounced cell line-dependent variability in HEV release pathways, emphasizing the importance of cellular context in studies of HEV biology and antiviral strategies targeting virus egress.</p>\",\"PeriodicalId\":12458,\"journal\":{\"name\":\"Frontiers in Cellular and Infection Microbiology\",\"volume\":\"15 \",\"pages\":\"1661270\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2025-09-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446258/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Cellular and Infection Microbiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fcimb.2025.1661270\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Cellular and Infection Microbiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fcimb.2025.1661270","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Cell line-dependent release of quasi-enveloped hepatitis E virus reveals alternative Golgi-associated egress in the absence of pORF3.
Background: Hepatitis E virus (HEV) particles are released from infected cells in a quasi-enveloped form, typically via the multivesicular body (MVB) pathway, which is mediated by the viral accessory protein pORF3. However, cell-type specific aspects of this release mechanism remain poorly understood.
Methods: We analyzed the release and envelopment characteristics of a pORF3-deficient genotype 3c HEV (HEVΔORF3) in comparison to wild-type HEV (HEVwt) in two human cell lines: hepatoma-derived PLC/PRF/5 and lung carcinoma-derived A549/D3 cells.
Results: While viral release of HEVΔORF3 was strongly impaired in A549/D3 cells, PLC/PRF/5 cells supported efficient viral release despite the absence of pORF3. In PLC/PRF/5 cells, HEV particles retained quasi-envelopment and utilized an alternative, Golgi-associated egress pathway in the absence of pORF3. In contrast, A549/D3 cells did not support this compensatory release route.
Conclusion: Our findings highlight a pronounced cell line-dependent variability in HEV release pathways, emphasizing the importance of cellular context in studies of HEV biology and antiviral strategies targeting virus egress.
期刊介绍：
Frontiers in Cellular and Infection Microbiology is a leading specialty journal, publishing rigorously peer-reviewed research across all pathogenic microorganisms and their interaction with their hosts. Chief Editor Yousef Abu Kwaik, University of Louisville is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
Frontiers in Cellular and Infection Microbiology includes research on bacteria, fungi, parasites, viruses, endosymbionts, prions and all microbial pathogens as well as the microbiota and its effect on health and disease in various hosts. The research approaches include molecular microbiology, cellular microbiology, gene regulation, proteomics, signal transduction, pathogenic evolution, genomics, structural biology, and virulence factors as well as model hosts. Areas of research to counteract infectious agents by the host include the host innate and adaptive immune responses as well as metabolic restrictions to various pathogenic microorganisms, vaccine design and development against various pathogenic microorganisms, and the mechanisms of antibiotic resistance and its countermeasures.
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