ArticleJournal of biomedical science2022
Hepatitis B virus virion secretion is a CRM1-spike-mediated late event.
Article in Journal of biomedical science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Review
- HBc: the multifunctional architect of HBV replication, immune evasion, and therapeutic innovation.Frontiers in immunology · 2025Review
- Hepatitis B virus entry, assembly, and egress.Microbiology and molecular biology reviews : MMBR · 2024Review
- Epitranscriptomic cytidine methylation of the hepatitis B viral RNA is essential for viral reverse transcription and particle production.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Significance of hepatitis B virus capsid dephosphorylation via polymerase.Journal of biomedical science · 2024Article
- Hepatitis B Core Antibody Level: A Surrogate Marker for Host Antiviral Immunity in Chronic Hepatitis B Virus Infections.Viruses · 2023Review
- Article
- Molecular elucidation of drug-induced abnormal assemblies of the hepatitis B virus capsid protein by solid-state NMR.Nature communications · 2023Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundHepatitis B virus (HBV) is a major human pathogen worldwide. To date, there is no curative treatment for chronic hepatitis B. The mechanism of virion secretion remains to be investigated. Previously, we found that nuclear export of HBc particles can be facilitated via two CRM1-specific nuclear export signals (NES) at the spike tip.
methodsIn this study, we used site-directed mutagenesis at the CRM1 NES, as well as treatment with CRM1 inhibitors at a low concentration, or CRM1-specific shRNA knockdown, in HBV-producing cell culture, and measured the secretion of various HBV viral and subviral particles via a native agarose gel electrophoresis assay. Separated HBV particles were characterized by Western blot analysis, and their genomic DNA contents were measured by Southern blot analysis. Secreted extracellular particles were compared with intracellular HBc capsids for DNA synthesis and capsid formation. Virion secretion and the in vivo interactions among HBc capsids, CRM1 and microtubules, were examined by proximity ligation assay, immunofluorescence microscopy, and nocodazole treatment.
resultsWe report here that the tip of spike of HBV core (HBc) particles (capsids) contains a complex sensor for secretion of both HBV virions and naked capsids. HBV virion secretion is closely associated with HBc nuclear export in a CRM1-dependent manner. At the conformationally flexible spike tips of HBc particles, NES motifs overlap extensively with motifs important for secretion of HBV virions and naked capsids.
conclusionsWe provided experimental evidence that virions and naked capsids can egress via two distinct, yet overlapping, pathways. Unlike the secretion of naked capsids, HBV virion secretion is highly CRM1- and microtubule-dependent. CRM1 is well known for its involvement in nuclear transport in literature. To our knowledge, this is the first report that CRM1 is required for virion secretion. CRM1 inhibitors could be a promising therapeutic candidate for chronic HBV patients in clinical medicine.
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