bims-nucpor 2023-12-10 papers

Issue of 2023‒12‒10
two papers selected by
Sara Mingu, Johannes Gutenberg University

Bioessays. 2023 Dec 03. e2300182

Nuclear envelope budding: Getting large macromolecular complexes out of the nucleus.

Kevin C Sule, Mitsutoshi Nakamura, Susan M Parkhurst.

Transport of macromolecules from the nucleus to the cytoplasm is essential for nearly all cellular and developmental events, and when mis-regulated, is associated with diseases, tumor formation/growth, and cancer progression. Nuclear Envelope (NE)-budding is a newly appreciated nuclear export pathway for large macromolecular machineries, including those assembled to allow co-regulation of functionally related components, that bypasses canonical nuclear export through nuclear pores. In this pathway, large macromolecular complexes are enveloped by the inner nuclear membrane, transverse the perinuclear space, and then exit through the outer nuclear membrane to release its contents into the cytoplasm. NE-budding is a conserved process and shares many features with nuclear egress mechanisms used by herpesviruses. Despite its biological importance and clinical relevance, little is yet known about the regulatory and structural machineries that allow NE-budding to occur in any system. Here we summarize what is currently known or proposed for this intriguing nuclear export process.

Keywords: Pavarotti; Torsin; Tumbleweed; WASH; actin bundling; actin nucleation; dFz2C; nuclear exit; vesicle-mediated nucleocytoplasmic transport; wash regulatory complex

DOI: https://doi.org/10.1002/bies.202300182

Sci Rep. 2023 Dec 04. 13(1): 21392

A computational spatial whole-Cell model for hepatitis B viral infection and drug interactions.

Zhaleh Ghaemi, Oluwadara Nafiu, Emad Tajkhorshid, Martin Gruebele, Jianming Hu.

Despite a vaccine, hepatitis B virus (HBV) remains a world-wide source of infections and deaths. We develop a whole-cell computational platform combining spatial and kinetic models describing the infection cycle of HBV in a hepatocyte host. We simulate key parts of the infection cycle with this whole-cell platform for 10 min of biological time, to predict infection progression, map out virus-host and virus-drug interactions. We find that starting from an established infection, decreasing the copy number of the viral envelope proteins shifts the dominant infection pathway from capsid secretion to re-importing the capsids into the nucleus, resulting in more nuclear-localized viral covalently closed circular DNA (cccDNA) and boosting transcription. This scenario can mimic the consequence of drugs designed to manipulate viral gene expression. Mutating capsid proteins facilitates capsid destabilization and disassembly at nuclear pore complexes, resulting in an increase in cccDNA copy number. However, excessive destabilization leads to premature cytoplasmic disassembly and does not increase the cccDNA counts. Finally, our simulations can predict the best drug dosage and its administration timing to reduce the cccDNA counts. Our adaptable computational platform can be parameterized to study other viruses and identify the most central viral pathways that can be targeted by drugs.

DOI: https://doi.org/10.1038/s41598-023-45998-0