The role of nuclear pores and importins for herpes simplex virus infection

Döhner, Katinka; Serrero, Manutea C; Sodeik, Beate

doi:10.1016/j.coviro.2023.101361

Cited by 9 publications

(4 citation statements)

References 189 publications

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“…We performed RNA interference (RNAi) knock down (KD) experiments to evaluate functional relevance of candidate MX2-interacting proteins on MX2-mediated restriction of HIV-1 and HSV-1 using doxycycline-inducible MX2 HeLa(MX2) cells. We selected 12 genes based on enrichment in our screening and/or their reported roles for nuclear targeting of incoming HIV-1 or HSV-1 capsids 46,47 (Figure S3A). KD of SAMD4A, TNPO1, or NUP35 impaired MX2-mediated restriction of HSV-1 and HIV-1.…”

Section: Resultsmentioning

confidence: 99%

MX2 restricts HIV-1 and herpes simplex virus type 1 by forming cytoplasmic biomolecular condensates that mimic nuclear pore complexes

Moschonas,

Delhaye,

Cooreman

et al. 2023

Preprint

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Human myxovirus resistance 2 (MX2) can potently restrict HIV-1 and herpesviruses at a post-entry step by a process that requires MX2 interaction with the capsids of these viruses. The involvement of other host cell factors in this process, however, remains poorly understood. Here, we mapped the proximity interactome of MX2 revealing strong enrichment of phenylalanine-glycine (FG)-rich proteins related to the nuclear pore complex as well as proteins that are part of cytoplasmic ribonucleoprotein granules. MX2 interacts with these proteins to form multiprotein cytoplasmic biomolecular condensates that are essential for its anti-HIV-1 and -herpes simplex virus-1 (HSV-1) activity. MX2 condensate formation requires the disordered N-terminal region of MX2 and its dimerization. We also demonstrate that incoming HIV-1 and HSV-1 capsids associate with MX2 at dynamic cytoplasmic biomolecular condensates. Our results reveal that MX2 forms nuclear pore-mimicking cytoplasmic condensates that act as nuclear pore decoys, thereby interfering with nuclear entry of HIV-1 and HSV-1.

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Section: Resultsmentioning

confidence: 99%

MX2 restricts HIV-1 and herpes simplex virus type 1 by forming cytoplasmic biomolecular condensates that mimic nuclear pore complexes

Moschonas,

Delhaye,

Cooreman

et al. 2023

Preprint

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“…The finding that kinesin-like protein Pav is involved in NEbudding opens the possibility that Pav and/or other motor proteins in the nucleus might contribute to forming different megaRNPs through their cargo domain binding to specific RNAs and proteins. [11,94] [2] While NE budding is observed in different species, it is not yet clear how similar the molecular machineries are among these contexts. Indeed, ESCRT proteins are required to release the bud from the nucleus in mammalian cell lines, [50] whereas NE budding in yeast does not require them.…”

Section: Discussionmentioning

confidence: 99%

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

Sule,

Nakamura,

Parkhurst

2023

BioEssays

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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.

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“…Various models for the trafficking of FG-Nups have been suggested, including the spider cobweb, forest, virtual gating, polymer brush, and selective phase/hydrogel models [19,30]. The malfunctioning of the NPC transport mechanism is linked to a variety of illnesses, including neurodegeneration [31], viral infections [32][33][34][35][36][37], and cancer [38,39].…”

Section: Introductionmentioning

confidence: 99%

An Efficient Method for Isolating and Purifying Nuclei from Mice Brain for Single-Molecule Imaging Using High-Speed Atomic Force Microscopy

Qiu,

Sajidah,

Kondo

et al. 2024

Cells

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Nuclear pore complexes (NPCs) on the nuclear membrane surface have a crucial function in controlling the movement of small molecules and macromolecules between the cell nucleus and cytoplasm through their intricate core channel resembling a spiderweb with several layers. Currently, there are few methods available to accurately measure the dynamics of nuclear pores on the nuclear membranes at the nanoscale. The limitation of traditional optical imaging is due to diffraction, which prevents achieving the required resolution for observing a diverse array of organelles and proteins within cells. Super-resolution techniques have effectively addressed this constraint by enabling the observation of subcellular components on the nanoscale. Nevertheless, it is crucial to acknowledge that these methods often need the use of fixed samples. This also raises the question of how closely a static image represents the real intracellular dynamic system. High-speed atomic force microscopy (HS-AFM) is a unique technique used in the field of dynamic structural biology, enabling the study of individual molecules in motion close to their native states. Establishing a reliable and repeatable technique for imaging mammalian tissue at the nanoscale using HS-AFM remains challenging due to inadequate sample preparation. This study presents the rapid strainer microfiltration (RSM) protocol for directly preparing high-quality nuclei from the mouse brain. Subsequently, we promptly utilize HS-AFM real-time imaging and cinematography approaches to record the spatiotemporal of nuclear pore nano-dynamics from the mouse brain.

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The role of nuclear pores and importins for herpes simplex virus infection

Cited by 9 publications

References 189 publications

MX2 restricts HIV-1 and herpes simplex virus type 1 by forming cytoplasmic biomolecular condensates that mimic nuclear pore complexes

MX2 restricts HIV-1 and herpes simplex virus type 1 by forming cytoplasmic biomolecular condensates that mimic nuclear pore complexes

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

An Efficient Method for Isolating and Purifying Nuclei from Mice Brain for Single-Molecule Imaging Using High-Speed Atomic Force Microscopy

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