Amphisome plays a role in HBV production and release through the endosomal and autophagic pathways Article Swipe
Jia Li
,
Thekla Kemper
,
Ruth Broering
,
Yong Lin
,
Xueyu Wang
,
Mengji Lu
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1097/hc9.0000000000000654
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1097/hc9.0000000000000654
Background: Autophagic and endosomal pathways coordinately contribute to HBV virions and subviral particles (SVPs) production. To date, limited evidence supports that HBV and exosomes have a common pathway for their biogenesis and secretion. The final steps of HBV production and release have not yet been well studied. Methods: We examined the production and release of HBV virions and SVPs by using GW4869 (N,N’-Bis[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-3,3’-pht hal amide dihydrochloride), a small molecule inhibiting ceramide-mediated inward membrane budding. Neutral sphingomyelinase, the target of GW4869, and RAB27A and –B, 2 small GTPases involved in exosome release control, were silenced using gene silencing to confirm the results obtained. Western blot, immunofluorescence staining, and confocal microscopy were applied. Results: GW4869 inhibited HBV virion release, causing their accumulation along with SVPs in hepatocytes. This triggered cellular endoplasmic reticulum stress, leading to protein kinase B-mechanistic target of rapamycin kinase signaling pathway inactivation. GW4869 treatment increased autophagosome formation and impaired autophagic degradation by blocking autophagosome-lysosome fusion. Consequently, HBsAg is increasingly localized to autophagosomes and late endosomes/multivesicular bodies. Silencing neutral sphingomyelinase yielded consistent results. Similarly, RAB27A silencing inhibited HBV virion and SVP secretion, causing their accumulation within hepatoma cells. Notably, GW4869 treatment, as well as RAB27A and -B silencing, increased the presence of LC3 + CD63 + HBsAg + complexes. Conclusions: Our results demonstrate the involvement of the autophagosome-late endosome/multivesicular bodies-exosome axis in regulating HBV production and release, highlighting amphisomes as a potential platform for HBV release.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1097/hc9.0000000000000654
- OA Status
- gold
- Cited By
- 1
- References
- 34
- Related Works
- 10
- OpenAlex ID
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All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4408406828Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1097/hc9.0000000000000654Digital Object Identifier
- Title
-
Amphisome plays a role in HBV production and release through the endosomal and autophagic pathwaysWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-03-13Full publication date if available
- Authors
-
Jia Li, Thekla Kemper, Ruth Broering, Yong Lin, Xueyu Wang, Mengji LuList of authors in order
- Landing page
-
https://doi.org/10.1097/hc9.0000000000000654Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1097/hc9.0000000000000654Direct OA link when available
- Concepts
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Endosome, Cell biology, Gene silencing, Autophagosome, Lysosome, Endoplasmic reticulum, Autophagy, Biology, Chemistry, Biochemistry, Intracellular, Enzyme, Gene, ApoptosisTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
1Total citation count in OpenAlex
- Citations by year (recent)
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2025: 1Per-year citation counts (last 5 years)
- References (count)
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34Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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