The only in vivo studies involving TNTs Tiwari is aware of have happened in the eye. As a result, TNT-mediated viral infection in vivo just “isn’t well documented,” explains Tiwari. And since TNTs are made of just actin, there are very few biomarkers for these tiny structures, making them difficult to study and distinguish from other actin-based protrusions. Studying TNTs in humans requires difficult-to-find, high-quality post-mortem tissue, which then needs to be imaged at super-high resolution. “This can be very challenging because TNTs are ephemeral structures and catching them in action can be difficult.” “Further studies are necessary to establish if the same mechanism operates in the animal or human brain,” says Margolzata Kloc, a biochemist at Houston Methodist Medical Research Institute who was not involved in the study. “They didn’t really answer that.”Īvindra Nath, a neurologist at the National Institutes of Health who was not involved in the study, similarly notes that while many cells make TNTs in culture, such structures may not occur in vivo. “Are blood-brain barrier cells capable of inducing these bridges?” he asks. They also didn’t directly show that blood-brain barrier cells could form TNTs and transfer the virus to neurons. However, Tiwari points out that while the study did show a potential way that neurons could be infected, the researchers didn’t show evidence that ACE2-positive cells could infect the types of epithelial cells that compose the blood-brain barrier. And given the fact that SARS-CoV-2 was infecting such a broad array of cell types, she thought maybe the coronavirus could similarly exploit TNTs. From previous work, Pasteur Institute cell biologist Chiara Zurzolo knew that some viruses use nanotubes to spread from cell to cell. Through the tubes, which are made of the protein actin, cells can send and receive RNA, nutrients, even entire organelles-and, unfortunately, viruses. Tunneling nanotubes (TNTs) are delicate, hairlike structures that sprout from the cell body and pierce through neighboring cell membranes when cells are stressed, including when they’re low on oxygen or during infection. Totally fascinating.” See “ Cancer Cell Nanotubes Hijack Mitochondria from Immune Sentinels” “They are saying that the virus can be transferred and it’s most likely through these bridges. “It’s a pretty exciting study,” Viabhav Tiwari, a virologist at Midwestern University who wasn’t involved in the research, tells The Scientist.
![em and sprout em and sprout](https://images-na.ssl-images-amazon.com/images/I/71f8S%2Bqqh4L._AC_SL1500_.jpg)
![em and sprout em and sprout](http://3.bp.blogspot.com/-H3P_Om4pnnY/T6HAvd2qATI/AAAAAAAAAy8/BofFtWdx82E/s1600/IMG_0077.jpg)
Now, a study published yesterday (July 20) in Science Advances suggests that the virus may be shuttling itself through tiny tubes that extend from infected host cells. Scientists have wondered how the virus is able to enter such unwelcoming tissues. But although many cells-including neurons and cells that make up the blood-brain barrier-lack this protein, bits of the virus have been found in the brains of infected people post-mortem. SARS-CoV-2 usually infects cells by binding with the angiotensin-2 converting enzyme receptor.
![em and sprout em and sprout](https://spookylittlehalloween.com/wp-content/uploads/2020/08/em-sprout-poison-apple-pin.jpg)
ABOVE: Fluorescent epithelial and neuronal cells in culture connected by tunneling nanotubes Anna Pepe, Institut Pasteur