Uncoating of non-enveloped viruses

Suomalainen, Maarit; Greber, Urs F.

doi:10.1016/j.coviro.2012.12.004

Cited by 103 publications

(84 citation statements)

References 76 publications

(66 reference statements)

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“…Non-enveloped viruses are membrane-free, except for certain picornaviruses which occur in both enveloped and non-enveloped forms [42]. They all encode membrane-interacting proteins, which are typically encased in a capsid, and can be activated or exposed by cues from the host cell during entry [35] [43]. Activation of membrane-active proteins leads to pore formation, piercing or rupture of the host membrane [44] [45] [46].…”

Section: Resultsmentioning

confidence: 99%

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

Luisoni

Bauer

Bartenschlager

et al. 2016

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Enveloped viruses fuse with host membranes without affecting cell integrity. Nonenveloped viruses and bacteria penetrate by rupturing endosomal membranes and thus 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, immunolabeling, confocal and electron microscopy, we detected robust signals from Gal3-containing, early endosomal antigen 1-positive membranes 1 h post-infection (pi). Adenoviruses penetrate from non-acidic endosomes with high efficiency, 15 min 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 3 h 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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Section: Resultsmentioning

confidence: 99%

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

Luisoni

Bauer

Bartenschlager

et al. 2016

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“…In contrast to ASFV and VV, Adv is a nonenveloped virus that relies mainly on mechanical cues for uncoating (57). With the Adv 2 and 5 serotypes, uncoating starts at receptor binding.…”

Section: Discussionmentioning

confidence: 99%

Cholesterol Flux Is Required for Endosomal Progression of African Swine Fever Virions during the Initial Establishment of Infection

Cuesta-Geijo

Chiappi

Galindo

et al. 2016

J Virol

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African swine fever virus (ASFV) is a major threat for porcine production that has been slowly spreading in Eastern Europe since its first appearance in the Caucasus in 2007. ASFV enters the cell by endocytosis and gains access to the cytosol to start replication from late endosomes and multivesicular bodies. Cholesterol associated with low-density lipoproteins entering the cell by endocytosis also follows a trafficking pathway similar to that of ASFV. Here we show that cholesterol plays an essential role in the establishment of infection as the virus traffics through the endocytic pathway. In contrast to the case for other DNA viruses, such as vaccinia virus or adenovirus 5, cholesterol efflux from endosomes is required for ASFV release/entry to the cytosol. Accumulation of cholesterol in endosomes impairs fusion, resulting in retention of virions inside endosomes. ASFV also remodels intracellular cholesterol by increasing its cellular uptake and redistributes free cholesterol to viral replication sites. Our analysis reveals that ASFV manipulates cholesterol dynamics to ensure an appropriate lipid flux to establish productive infection. IMPORTANCESince its appearance in the Caucasus in 2007, African swine fever (ASF) has been spreading westwards to neighboring European countries, threatening porcine production. Due to the lack of an effective vaccine, ASF control relies on early diagnosis and widespread culling of infected animals. We investigated early stages of ASFV infection to identify potential cellular targets for therapeutic intervention against ASF. The virus enters the cell by endocytosis, and soon thereafter, viral decapsidation occurs in the acid pH of late endosomes. We found that ASFV infection requires and reorganizes the cellular lipid cholesterol. ASFV requires cholesterol to exit the endosome to gain access to the cytoplasm to establish productive replication. Our results indicate that there is a differential requirement for cholesterol efflux for vaccinia virus or adenovirus 5 compared to ASFV.

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“…Cell-based assays suggested that disassembly starts at the cell surface by mechanical forces executed through differential receptor binding, releasing fiber and inducing conformational changes in pentons through integrin binding, ultimately allowing protein VI release, although it remains unclear how disassembly and protein VI release are linked (1,2,30,31).…”

mentioning

confidence: 99%

“…Productive infection of new cells requires that the capsid follow a stepwise disassembly process upon entry that, if perfectly executed, results in highly efficient genome transfer to the nucleus (1,2).…”

mentioning

confidence: 99%

The Amphipathic Helix of Adenovirus Capsid Protein VI Contributes to Penton Release and Postentry Sorting

Martinez

Schellenberger

Vasishtan

et al. 2015

J Virol

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Nuclear delivery of the adenoviral genome requires that the capsid cross the limiting membrane of the endocytic compartment and traverse the cytosol to reach the nucleus. This endosomal escape is initiated upon internalization and involves a highly coordinated process of partial disassembly of the entering capsid to release the membrane lytic internal capsid protein VI. Using wild-type and protein VI-mutated human adenovirus serotype 5 (HAdV-C5), we show that capsid stability and membrane rupture are major determinants of entry-related sorting of incoming adenovirus virions. Furthermore, by using electron cryomicroscopy, as well as penton-and protein VI-specific antibodies, we show that the amphipathic helix of protein VI contributes to capsid stability by preventing premature disassembly and deployment of pentons and protein VI. Thus, the helix has a dual function in maintaining the metastable state of the capsid by preventing premature disassembly and mediating efficient membrane lysis to evade lysosomal targeting. Based on these findings and structural data from cryo-electron microscopy, we suggest a refined disassembly mechanism upon entry. IMPORTANCEIn this study, we show the intricate connection of adenovirus particle stability and the entry-dependent release of the membrane-lytic capsid protein VI required for endosomal escape. We show that the amphipathic helix of the adenovirus internal protein VI is required to stabilize pentons in the particle while coinciding with penton release upon entry and that release of protein VI mediates membrane lysis, thereby preventing lysosomal sorting. We suggest that this dual functionality of protein VI ensures an optimal disassembly process by balancing the metastable state of the mature adenovirus particle.A denoviruses (AdVs) are nonenveloped, double-stranded DNA viruses that assemble in the nuclei of productively infected cells and are released at the end of the infection cycle into the extracellular milieu. Productive infection of new cells requires that the capsid follow a stepwise disassembly process upon entry that, if perfectly executed, results in highly efficient genome transfer to the nucleus (1, 2).The AdV virion is composed of 13 different polypeptides that form an icosahedral capsid encompassing the genome-containing viral core. The capsid is mainly composed of trimeric hexons building up the facets of the capsid. Pentons and fibers are located at each of the 12 vertices, where they form a pentameric penton base from which the trimeric fiber molecule elongates (3-5). In addition the capsid is stabilized via the cement proteins IIIa, VI, VIII, and IX. The capsid encloses the viral core, with the viral genome organized into chromatin through association with the major core protein VII and proteins V, X, TP, and IVa2 (3-5). Following (or concomitant with) capsid assembly, several of the virion proteins undergo proteolytic processing by the virion-incorporated adenoviral proteinase (AVP) (6). This process of virus maturation is essential to render ne...

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Uncoating of non-enveloped viruses

Cited by 103 publications

References 76 publications

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

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

Cholesterol Flux Is Required for Endosomal Progression of African Swine Fever Virions during the Initial Establishment of Infection

The Amphipathic Helix of Adenovirus Capsid Protein VI Contributes to Penton Release and Postentry Sorting

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Uncoating of non-enveloped viruses

Cited by 103 publications

References 76 publications

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

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

Cholesterol Flux Is Required for Endosomal Progression of African Swine Fever Virions during the Initial Establishment of Infection

The Amphipathic Helix of Adenovirus Capsid Protein VI Contributes to Penton Release and Postentry Sorting

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

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