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SARS-CoV-2 hijacks nanotubes between neurons to infect them

SARS-CoV-2 hijacks nanotubes between neurons to infect them

SARS-CoV-2 viral particles (in dark blue) in and on the surface of a nanotube. Cryoelectron tomography images segmented using Amira software. Credit: © Anna Pepe, Institut Pasteur

COVID-19 often leads to neurological symptoms, such as loss of taste or smell, or cognitive impairment (including memory loss and difficulty concentrating), both during the acute phase of the disease and over the long term in ‘prolonged COVID’ syndrome. But the way the infection reaches the brain was previously unknown. Scientists from Institut Pasteur and CNRS labs have used advanced electron microscopy approaches to show that SARS-CoV-2 hijacks nanotubes, tiny bridges that connect infected cells to neurons. The virus is therefore able to invade neurons despite the fact that they lack the ACE2 receptor to which the virus normally binds when infecting cells.

How does SARS-CoV-2 enter brain cells? A recently published study in scientific progress shows that the virus uses nanotubes that form between infected cells and neurons to access neurons. These transient dynamic structures are the result of membrane fusion in distant cells. They allow the exchange of cellular material without the need for membrane receptors, the normal way to enter and exit the cytoplasm. The Membrane Traffic and Pathogenesis Unit, led by Chiara Zurzolo of the Institut Pasteur, has already discovered that nanotubes play a role in degenerative diseases such as Alzheimer’s and Parkinson’s by facilitating the transport of proteins responsible for these diseases.

Infecting neurons in the absence of a receptor

Although the human cell receptor ACE2 serves as a gateway for SARS-CoV-2 to enter lung cells – the main target of the virus – and cells in the olfactory epithelium, it is not expressed by neurons. But viral genetic material has been found in the brains of some patients, explaining the neurological symptoms characteristic of acute or long-term COVID. The olfactory mucosa has previously been suggested as a route to the central nervous system, but that doesn’t explain how the virus itself can enter neuronal cells.

According to this new study, SARS-CoV-2 would also be able to induce nanotube formation between infected cells and neurons, as well as between neurons, which would explain how the brain is infected from the epithelium. The research team revealed multiple viral particles that reside both inside and on the surface of nanotubes. Since the virus spreads faster and more directly from nanotubes than by leaving one cell to enter the next through a receptor, this mode of transmission therefore contributes to the infectious capacity of SARS-CoV-2 and its spread. to neuronal cells.

But the virus also moves on the outer surface of nanotubes, where it can be more quickly directed to cells that express compatible receptors. “Nanotubes can be seen as tunnels with a road on top,” said Chiara Zurzolo, head of the Membrane Traffic and Pathogenesis Department at the Institut Pasteur, “that allow the infection of non-permissive cells such as neurons, but also the spread of infection. between permissive cells.”

SARS-CoV-2 hijacks nanotubes between neurons to infect them

SARS-CoV-2 (in yellow) spreads between infected cells via nanotubes. 3D image of confocal microscopy produced using Imaris software. Credit: © Anna Pepe, Institut Pasteur

State-of-the-art imaging methods with the Titan Krios microscope

This publication combines research on in vitro cultures, showing that healthy neuronal cells become infected when they come into contact with infected cells, using state-of-the-art microscopy instruments. The Titan Krios microscope in the NanoImaging Core Facility at the Institut Pasteur provides unprecedented resolution of biological samples and nanomolecules that is closer to real biological conditions. “With this instrument, new imaging approaches have been developed to evaluate the structure of SARS-CoV-2 and the architecture of nanotubes,” explains Anna Pepe of the Institut Pasteur’s Membrane Traffic and Pathogenesis Unit, lead author of the study.

In collaboration with the Ultrastructural BioImaging Core Facility at the Institut Pasteur, the research teams used precise research methods to detect structures inside the nanotubes that were then identified as ‘virus factories’. The nanotubes between neurons provide a favorable environment for the development of SARS-CoV-2, because it is invisible to the immune system. Chiara Zurzolo believes that “it could be a mechanism for immune evasion and viral persistence that could be beneficial for the virus.”

This study is an example of how fundamental interdisciplinary research involving cell biologists, virologists and state-of-the-art imaging techniques can lead to new discoveries. It paves the way for further research into the role of cell-to-cell communication in the spread of SARS-CoV-2. It also stimulates the exploration of alternative therapeutic approaches to counter the spread of SARS-CoV-2, in addition to ongoing projects primarily aimed at blocking access through the ACE2 receptor.


Study suggests SARS-CoV-2 virus enters brain by using cells in nose to create nanotube tunnels


More information:
Anna Pepe et al, Tunneling nanotubes provide a pathway for SARS-CoV-2 propagation, scientific progress (2022). DOI: 10.1126/sciaadv.abo0171

Provided by Pasteur Institute


Quote: SARS-CoV-2 hijacks nanotubes between neurons to infect them (2022, July 25) retrieved July 26, 2022 from https://phys.org/news/2022-07-sars-cov-hijacks-nanotubes-neurons- infection. html

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