ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Molecular Viral Pathogenesis
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1661270
Cell line-dependent release of quasi-enveloped hepatitis E virus reveals alternative Golgi-associated egress in the absence of pORF3
Provisionally accepted
Nele Gremmel1
Mirco Glitscher2Johannes Scholz3Ashish Gadicherla3,4
Reimar Johne3
Eberhard Hildt2,5*
Paul Becher1*- 1University of Veterinary Medicine Hannover, Institute of Virology, Department of Infectious Diseases, Hanover, Germany
- 2Paul-Ehrlich-Institute, Department of Virology, Langen, Germany
- 3German Federal Institute for Risk Assessment, Department of Biological Safety, Berlin, Germany
- 4Deptartment of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, United States
- 5Hasso-Plattner-Institute, Digital Health Cluster, Potsdam, Germany
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Background: Hepatitis E virus (HEV) particles are released from infected cells in a quasienveloped 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.We analyzed the release and envelopment characteristics of a pORF3-deficient genotype 3c HEV (HEV∆ORF3) 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 HEV∆ORF3 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.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.
Keywords: Hepatitis E virus, Cellular release mechanisms, quasi-envelopment, Golgi-associated release, Molecular Virology, ORF3-protein
Received: 07 Jul 2025; Accepted: 14 Aug 2025.
Copyright: © 2025 Gremmel, Glitscher, Scholz, Gadicherla, Johne, Hildt and Becher. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Eberhard Hildt, Paul-Ehrlich-Institute, Department of Virology, Langen, Germany
Paul Becher, University of Veterinary Medicine Hannover, Institute of Virology, Department of Infectious Diseases, Hanover, Germany
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