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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.
Highlights
All viruses and many bacteria that enter eukaryotic cells activate a genetic program for replication and immune evasion [2] [3] [4]
The data show that broken early endosomes but not virus particles are rapidly removed by a process involving autophagy, which we term ‘endosomophagy’
The observation here shows that adenovirus ruptured early endosomal membranes are targeted for clearance
Summary
All viruses and many bacteria that enter eukaryotic cells activate a genetic program for replication and immune evasion [2] [3] [4]. Damage to host cells occurs during invasion of bacteria and non-enveloped viruses, including Salmonella, Shigella, Listeria or Adenovirus, which disrupt phagocytic vacuoles and endosomes [8] [9]. Disrupted vacuoles recruit beta-galactoside binding lectins, such as galectin-3 (Gal3) and Gal, both widely expressed in epithelial cells [10] [11] [12] [13]. Cytosolic galectins can be subject to export by leader peptide-independent mechanisms [14] [15] [16]. They can bind to enveloped viruses and bacteria, and act as pattern recognition receptors [17]. Intracellular Gal coordinates the destruction of disrupted late endosomes and associated bacteria by autophagy, whereas Gal is involved in membrane sorting by clustering glycoproteins and glycolipids, and modulation of cell-cell contacts during organogenesis [18] [19] [20]
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