A mystery about how the novel coronavirus reaches the brain has always puzzled scientists.
But a new study has now revealed how the virus, that causes the Covid-19 disease, hijacks tiny nanotube bridges that link infected cells with neurons and thus infects the brain.
The research, published in the journal Science Advances last week, reveals how the pathogen penetrates neurons despite them lacking the key “gateway” ACE2 receptor the virus usually binds to when infecting cells.
Studies have shown that Covid is associated with several neurological symptoms.
These include the loss of taste or smell and cognitive impairments like memory loss and concentration difficulties, commonly called “brain fog”, both of which occur during the acute phase of the disease and over the long term with the “long Covid” syndrome.
The mechanism behind the viral infection reaching the brain, however, has remained a mystery.
In the new study, researchers from Institut Pasteur and CNRS laboratories in France used state-of-the-art electron microscopy approaches to show the Sars-CoV-2 – the scientific name for the novel coronavirus – hijacks the nanotubes.
Scientists showed healthy neuronal cells are infected if they come into contact with infected cells.
These nanotubes are transient dynamic structures that are a result of membrane fusion in distant cells, enabling the exchange of cellular material without the need for special receptors on cells – the normal means of entering and exiting a cell’s cytoplasm.
Nanotubes have previously been found to play a role in degenerative diseases such as Alzheimer’s and Parkinson’s by facilitating the transport of proteins responsible for these diseases.
While several studies since the origin of the Covid pandemic have shown ACE2 serves as a entry gate for the coronavirus to enter lung cells – the main target of the virus – it has remained a mystery how the neurons, which do not express this gateway protein, are infected.
Researchers have also found viral genetic material in the brains of some patients, explaining the neurological symptoms linked with acute or long Covid.
The new study shows that the coronavirus could induce the formation of nanotubes between infected cells and neurons as well as among neurons – findings that explain how the brain is infected.
Scientists revealed multiple viral particles located both inside and on the surface of nanotubes.
Since the virus spreads more rapidly and directly from within nanotubes than by exiting one cell to move to the next via a receptor, researchers said this mode of transmission contributes to the infectious capacity of the coronavirus and its spread to nerve cells.
The virus can also move on the external surface of nanotubes, where it can be guided more quickly to cells that express compatible receptors.
“Nanotubes can be seen as tunnels with a road on top, which enable the infection of nonpermissive cells like neurons but also facilitate the spread of infection between permissive cells,” study co-author Chiara Zurzolo from Institut Pasteur said in a statement.
Researchers suspect the nanotubes between nerve cells represent a convenient environment for the coronavirus to develop as it is invisible to the immune system.
“It may represent a mechanism for immune evasion and viral persistence that could be favorable to the virus,” Dr Zurzolo said.
The findings, scientists hope, would lead to the discovery of alternative therapeutic approaches to hinder the spread of the virus, alongside other research focused on blocking its entry through the ACE2 receptor.
