Quiz solved? For a long time it was unclear how the corona virus can penetrate the actually insensitive brain cells. Now a study reveals their trick. Accordingly, SARS-CoV-2 uses neuronal nanotubes to get into the brain cells.
These connecting lines between cells lead directly into the interior of the neurons – and thus enable the pathogen to get from the susceptible cells to the actually non-susceptible neurons. In addition, the corona virus promotes the formation of such nanotunnels and thus facilitates the spread.
Neurological symptoms show that the SARS-CoV-2 coronavirus also affects the brain and nervous system. Many Long-Covid patients suffer from memory and concentration disorders as well as cognitive deficits, and the brain metabolism is also disturbed in some of those affected by Neuro-Covid.
Studies with brain organoids have already shown that the virus can multiply in neurons, and coronavirus particles have also been detected in the brains of patients who died with Covid-19.
The question, however, is how the coronavirus gets into the brain cells. Although the nose and olfactory nerve represent an entry point into the brain, the neurons themselves are actually not that easy for the virus to crack. In contrast to many other body cells, the ACE2 receptor on neurons required for the virus to penetrate is often missing or only present in very small numbers. “Therefore, it is not yet clear how the virus can spread in the brain,” explain Anna Pepe from the Pasteur Institute in Paris and her colleagues.
In order to clarify this question, the team followed a new lead: They investigated what role intercellular nanotunnels could play. “Nanotunnels are thin, membranous and actin-containing conduits that enable the direct transport of cellular cargo such as organelles, amyloid proteins and also virus particles between distant cells,” the researchers explain. Because these tunnels lead into the interior of the connected cells, these “cargo pieces” do not first have to pass through membrane channels or receptors on the cell surface.
This is exactly what the corona virus takes advantage of, as Pepe and her colleagues have now found out. For their study, they first added SARS-CoV-2 to the nutrient solution of a neuron cell culture. As expected, the viruses did not manage to penetrate the brain cells – they lacked the portal of entry in the form of the ACE2 receptor. “This confirms that neuronal cells cannot be infected through a receptor-based mechanism,” explains the team.
However, this was different when the neurons were cultured together with virus-susceptible epithelial cells: 24 hours after the addition of SARS-CoV-2, a third of the brain cells were already infected with the coronavirus, after 48 hours it was up to 62 percent. “Neural cells can therefore be infected with the coronavirus if they occur together with susceptible cell types,” write Pepe and her colleagues.
Further analysis revealed that nanotunnels had formed between the different cells. In these, the researchers were able to detect both complete virus particles and the SARS-CoV-2 replication complexes formed by proteins. The coronavirus can therefore use these cellular tunnels to get from a vulnerable, infected cell to cell types that are not normally accessible.
This direct, receptor-independent transport was also confirmed by a supplementary test in which the researchers blocked all ACE2 docking sites with an antibody. After 48 hours, in the co-culture permeated by nanotunnels, just as many neurons were infected with the coronavirus as in untreated control cultures. “This confirms that SARS-CoV-2 can penetrate non-permissive cells through direct cell-to-cell contact,” say Pepe and her team.
These results could therefore explain how the corona virus can also affect our brain cells. Apparently, it uses the nanotunnels that reach from the other cell types in the brain to the neurons. And not only that: As the tests showed, the virus promotes the formation of such connecting tunnels and makes them more stable and longer. In infected mixed cultures, the percentage of cells coupled via nanotunnels doubled, as the researchers found.
“In summary, we show that SARS-CoV-2 can hijack the nanotunnels to spread through the connected cells,” write Pepe and her colleagues. “This intercellular route could contribute to the pathogenesis of Covid-19 and also allow the virus access to the non-susceptible neuronal cells.”
And the corona virus benefits from something else: In these nanotunnels, the virus is invisible to our immune system. These hidden pathways could make it easier for SARS-CoV-2 to evade the immune system and stay in these tissues longer.
What: Pasteur Institute
This article was written by Nadja Podbregar
The original of this article “This is how corona can also get into brain cells” comes from scinexx.
