Cell line-dependent release of quasi-enveloped hepatitis E virus reveals alternative Golgi-associated egress in the absence of pORF3.

IF 4.8 2区医学 Q2 IMMUNOLOGY

Frontiers in Cellular and Infection Microbiology Pub Date : 2025-09-05 eCollection Date: 2025-01-01 DOI:10.3389/fcimb.2025.1661270

Nele Gremmel, Mirco Glitscher, Johannes Scholz, Ashish Gadicherla, Reimar Johne, Eberhard Hildt, Paul Becher

{"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":"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.","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}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

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。

背景：戊型肝炎病毒（HEV）颗粒以准包膜形式从感染细胞中释放，通常通过多泡体（MVB）途径释放，该途径由病毒辅助蛋白pORF3介导。然而，这种释放机制的细胞类型特异性方面仍然知之甚少。方法：我们在两种人类细胞系：肝癌来源的PLC/PRF/5和肺癌来源的A549/D3细胞中，分析了porf3缺陷基因型3c型HEV （HEVΔORF3）与野生型HEV （HEVwt）的释放和包膜特性。结果：虽然A549/D3细胞中HEVΔORF3的病毒释放严重受损，但PLC/PRF/5细胞在缺乏pORF3的情况下支持有效的病毒释放。在PLC/PRF/5细胞中，HEV颗粒保留了准包膜，并在缺乏pORF3的情况下利用另一种高尔基相关的出口途径。相反，A549/D3细胞不支持这种代偿释放途径。结论：我们的研究结果强调了HEV释放途径中明显的细胞系依赖性变异性，强调了细胞背景在HEV生物学研究和靶向病毒输出的抗病毒策略中的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Frontiers in Cellular and Infection Microbiology IMMUNOLOGY-MICROBIOLOGY

CiteScore

7.90

自引率

7.00%

发文量

1817

审稿时长

14 weeks

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.