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Membrane-assisted a...
Membrane-assisted assembly and selective secretory autophagy of enteroviruses
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- Dahmane, Selma (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Molekylär Infektionsmedicin, Sverige (MIMS)
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- Kerviel, Adeline (författare)
- Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, National Institutes of Health, MD, Bethesda, United States
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- Morado, Dustin R. (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, Stockholm, Sweden
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- Shankar, Kasturika (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Molekylär Infektionsmedicin, Sverige (MIMS)
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- Ahlman, Björn (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Molekylär Infektionsmedicin, Sverige (MIMS)
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- Lazarou, Michael (författare)
- Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, Australia
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- Altan-Bonnet, Nihal (författare)
- Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, National Institutes of Health, MD, Bethesda, United States
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- Carlson, Lars-Anders (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Molekylär Infektionsmedicin, Sverige (MIMS)
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(creator_code:org_t)
- 2022-10-10
- 2022
- Engelska.
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Enteroviruses are non-enveloped positive-sense RNA viruses that cause diverse diseases in humans. Their rapid multiplication depends on remodeling of cytoplasmic membranes for viral genome replication. It is unknown how virions assemble around these newly synthesized genomes and how they are then loaded into autophagic membranes for release through secretory autophagy. Here, we use cryo-electron tomography of infected cells to show that poliovirus assembles directly on replication membranes. Pharmacological untethering of capsids from membranes abrogates RNA encapsidation. Our data directly visualize a membrane-bound half-capsid as a prominent virion assembly intermediate. Assembly progression past this intermediate depends on the class III phosphatidylinositol 3-kinase VPS34, a key host-cell autophagy factor. On the other hand, the canonical autophagy initiator ULK1 is shown to restrict virion production since its inhibition leads to increased accumulation of virions in vast intracellular arrays, followed by an increased vesicular release at later time points. Finally, we identify multiple layers of selectivity in virus-induced autophagy, with a strong selection for RNA-loaded virions over empty capsids and the segregation of virions from other types of autophagosome contents. These findings provide an integrated structural framework for multiple stages of the poliovirus life cycle. Enteroviruses are non-enveloped positive-sense RNA viruses that modulate cytoplasmic membranes for replication. To enlighten how enteroviruses assemble around nascent RNA genomes and get package into autophagosomes for release, Dahmane et al. perform cryo-electron tomography of poliovirus-infected cells. They find assembly intermediates that are only present on the cytosolic side of the replication compartment and provide evidence that host factor VPS34 is involved in progression of assembly intermediates.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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