How Non-Cytolytic Enteroviruses May Spread From Cell to Cell

[knackers323]

@Hip ate you aware of any info regarding the rates that non cfsers test positive to high enterovirus antibodies?

 

[Gemini]

Gemini
What would 'negative' mean??[/QUOTE]
@perrier, we need to find out.

When Dr.Unger speaks/takes questions next, we can ask her if a paper is forthcoming, and if not, request the
CDC researchers who did the work (I don't think it was her department) provide us the details.

 

[Pyrrhus]

This study demonstrates a possible mechanism by which non-cytolytic enteroviruses may be able to spread into adjacent cells.

This study found that in CVB-infected cells, the virus seems to be able to create filament-like cellular protrusions that grow out of the cell, bridging to adjacent cells.

Cellular protrusions are a normal part of cellular function: they are created by the cell when it wants to gain traction and pull itself along in the tissues — this is basically how cells can move.

However, the authors suggest that these protrusions may be used by CVB in order to transmit the infection into adjacent cells. In other words, enterovirus may induce cellular protrusions to create a bridge to adjacent cells, which they then cross.

Similar cellular protrusions (now referred to as "Tunneling Nano-Tubes (TNT)") have now been observed with the coronavirus!

Tunneling nanotubes provide a route for SARS-CoV-2 spreading (Pepe et al., 2022)
https://doi.org/10.1126/sciadv.abo0171

Excerpt:

Neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection represent a major issue in long coronavirus disease. How SARS-CoV-2 gains access to the brain and how infection leads to neurological symptoms are not clear because the principal means of viral entry by endocytosis, the angiotensin-converting enzyme 2 receptor, are barely detectable in the brain.

We report that human neuronal cells, nonpermissive to infection through the endocytic pathway, can be infected when cocultured with permissive infected epithelial cells.

SARS-CoV-2 induces the formation of tunneling nanotubes (TNTs) and exploits this route to spread to uninfected cells. In cellulo correlative fluorescence and cryo–electron tomography reveal that SARS-CoV-2 is associated with TNTs between permissive cells.

Furthermore, multiple vesicular structures such as double-membrane vesicles, sites of viral replication, are observed inside TNTs between permissive and nonpermissive cells. Our data highlight a previously unknown mechanism of SARS-CoV-2 spreading, likely used as a route to invade nonpermissive cells and potentiate infection in permissive cells.

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[Hip]

Similar cellular protrusions (now referred to as "Tunneling Nano-Tubes (TNT)") have now been observed with the coronavirus!

Wow!

These tunneling nanotubes (TNT) could be interesting to look for in long COVID patients.

 

[Pyrrhus]

Someone pointed out to me an earlier paper that also observed this phenomenon:

An intra-cytoplasmic route for SARS-CoV-2 transmission unveiled by Helium-ion microscopy (Merolli et al., 2022)
https://doi.org/10.1038/s41598-022-07867-0

Excerpt:

SARS-CoV-2 virions enter the host cells by docking their spike glycoproteins to the membrane-bound Angiotensin Converting Enzyme 2. After intracellular assembly, the newly formed virions are released from the infected cells to propagate the infection, using the extra-cytoplasmic ACE2 docking mechanism.

However, the molecular events underpinning SARS-CoV-2 transmission between host cells are not fully understood. Here, we report the findings of a scanning Helium-ion microscopy study performed on Vero E6 cells infected with mNeonGreen-expressing SARS-CoV-2.

Our data reveal, with unprecedented resolution, the presence of: (1) long tunneling nanotubes that connect two or more host cells over submillimeter distances; (2) large scale multiple cell fusion events (syncytia); and (3) abundant extracellular vesicles of various sizes.

Taken together, these ultrastructural features describe a novel intra-cytoplasmic connection among SARS-CoV-2 infected cells that may act as an alternative route of viral transmission, disengaged from the well-known extra-cytoplasmic ACE2 docking mechanism. Such route may explain the elusiveness of SARS-CoV-2 to survive from the immune surveillance of the infected host.

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[Pyrrhus]

Related discussion:

Viral Extracellular Vesicles known as ‘Stealth Spheres’
https://forums.phoenixrising.me/threads/viral-extracellular-vesicles-known-as-stealth-spheres.75937/