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Endosomophagy clears disrupted early endosomes but not virus particles during virus entry into cells


Luisoni, Stefania; Bauer, Michael; Prasad, Vibhu; Boucke, Karin; Papadopoulos, Chrisovalantis; Meyer, Hemmo; Hemmi, Silvio; Suomalainen, Maarit; Greber, Urs F (2016). Endosomophagy clears disrupted early endosomes but not virus particles during virus entry into cells. Matters:online.

Abstract

Enveloped viruses fuse with host membranes without affecting cell integrity. Non-enveloped viruses and bacteria penetrate by rupturing endosomal membranes, and thereby expose complex-type carbohydrates from the endosome lumen to cytosolic proteins. Here we report on the dynamics and initial marker analyses of Galectin-3 (Gal3)-positive membranes triggered by incoming adenovirus species B/C in HeLa cells. Using mCherry-Gal3 reporter constructs, immuno-labeling, confocal and electron microscopy, we detected robust signals from Gal3-containing, early endosomal antigen 1-positive membranes 1h post-infection (pi). Adenoviruses penetrate from non-acidic endosomes with high efficiency, 15min pi, and largely outnumbered the Gal3-positive membranes, suggesting that Gal3 recruitment to broken membranes is transient, or Gal3-positive membranes are rapidly turned-over. In support of rapid turn-over, Gal3 was found within single membrane vesicles and degradative autophagosomes. The Gal3-membranes contained ubiquitin and the poly-ubiquitin binding protein p62/sequestosome-1, but only low amounts of virus, or membrane-lytic protein VI exposed from virions. Remarkably, the Gal3-positive membranes were cleared 3h pi, slower than protein VI, which was cleared 30 min pi. The data show that broken early endosomes but not virus particles are rapidly removed by a process involving autophagy, which we term ‘endosomophagy’. We speculate that endosomophagy is pro-viral, and attenuates innate immunity.

Abstract

Enveloped viruses fuse with host membranes without affecting cell integrity. Non-enveloped viruses and bacteria penetrate by rupturing endosomal membranes, and thereby expose complex-type carbohydrates from the endosome lumen to cytosolic proteins. Here we report on the dynamics and initial marker analyses of Galectin-3 (Gal3)-positive membranes triggered by incoming adenovirus species B/C in HeLa cells. Using mCherry-Gal3 reporter constructs, immuno-labeling, confocal and electron microscopy, we detected robust signals from Gal3-containing, early endosomal antigen 1-positive membranes 1h post-infection (pi). Adenoviruses penetrate from non-acidic endosomes with high efficiency, 15min pi, and largely outnumbered the Gal3-positive membranes, suggesting that Gal3 recruitment to broken membranes is transient, or Gal3-positive membranes are rapidly turned-over. In support of rapid turn-over, Gal3 was found within single membrane vesicles and degradative autophagosomes. The Gal3-membranes contained ubiquitin and the poly-ubiquitin binding protein p62/sequestosome-1, but only low amounts of virus, or membrane-lytic protein VI exposed from virions. Remarkably, the Gal3-positive membranes were cleared 3h pi, slower than protein VI, which was cleared 30 min pi. The data show that broken early endosomes but not virus particles are rapidly removed by a process involving autophagy, which we term ‘endosomophagy’. We speculate that endosomophagy is pro-viral, and attenuates innate immunity.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:7 August 2016
Deposited On:09 Aug 2016 10:18
Last Modified:10 Feb 2017 13:30
Publisher:ScienceMatters AG
ISSN:2297-8240
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.19185/matters.201606000013
Official URL:https://sciencematters.io/articles/201606000013

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