SARS-CoV-2 generally infects cells by binding with the angiotensin-2 converting enzyme receptor. Although lots of cells– including nerve cells and cells that make up the blood-brain barrier– lack this protein, bits of the virus have actually been discovered in the brains of contaminated individuals post-mortem. Researchers have actually wondered how the virus is able to get in such unwelcoming tissues. Now, a study published the other day (July 20) in Science Advances recommends that the virus may be shuttling itself through tiny tubes that extend from contaminated host cells.”Its a quite interesting research study,” Viabhav Tiwari, a virologist at Midwestern University who wasnt involved in the research study, tells The Scientist. “They are saying that the virus can be moved and its more than likely through these bridges … Totally remarkable.”See “Cancer Cell Nanotubes Hijack Mitochondria from Immune Sentinels”Tunneling nanotubes (TNTs) are fragile, hairlike structures that grow from the cell body and pierce through neighboring cell membranes when cells are stressed out, consisting of when theyre low on oxygen or during infection. Through televisions, which are made of the protein actin, cells can send out and get RNA, nutrients, even entire organelles– and, regrettably, viruses. From previous work, Pasteur Institute cell biologist Chiara Zurzolo knew that some infections use nanotubes to spread from cell to cell. And given the fact that SARS-CoV-2 was contaminating such a broad selection of cell types, she thought possibly the coronavirus could similarly make use of TNTs.”This virus is a monster. It infects everything,” Zurzolo states. “It spreads out extremely quick throughout the brain and we believe this is a possible mechanism” of how it does so.To test this line of thinking, the researchers cultured Vero E6 cells, which design the cells that line our skin, organs, and capillary– and reveal angiotensin-2 converting enzyme (ACE2). Individually, the team also cultured SH-SY5Y, which design human neuronal cells and lack the ACE2 receptor. As forecasted, the coronavirus easily contaminated the epithelial cells, but not the neurons. However when the scientists cultured contaminated epithelial cells and the neurons together with one another, they discovered viral proteins within the neurons after simply one day. The researchers found that when ACE2 receptors were blocked, the infection was still able to discover its way from infected epithelial cells to noninfected ones. See “SARS-CoV-2 Can Spread Via Cell-to-Cell Transmission”Fluorescent (top) and cryo-electron (bottom) microscopy images revealing SARS-CoV-2 inside and on top of tunneling nanotubesAnna Pepe, Institut PasteurUsing a mix of fluorescence confocal microscopy and cryo-electron microscopy (cryo-EM)– a technique that involves flash-freezing samples and bombarding them with electrons, allowing scientists to record 3D images of minuscule molecules– the scientists observed viral proteins and RNA within TNTs that were bridging cells. The TNTs likewise included double-membrane blisters, which are factories that churn out viral RNA. The researchers thought about these findings strong proof that the TNTs were acting as channels for viral transmission, likely permitting the infection to get and bypass the blood-brain barrier into the brain.However, Tiwari explains that while the study did reveal a potential manner in which nerve cells could be contaminated, the scientists didnt reveal proof that ACE2-positive cells could infect the kinds of epithelial cells that compose the blood-brain barrier. They likewise didnt directly show that blood-brain barrier cells could form TNTs and move the virus to neurons. “Are blood-brain barrier cells capable of inducing these bridges?” he asks. “They didnt truly respond to that.”Avindra Nath, a neurologist at the National Institutes of Health who was not associated with the research study, similarly keeps in mind that while many cells make TNTs in culture, such structures might not happen in vivo. “Further research studies are needed to develop if the very same mechanism [of TNTs shuttling SARS-CoV-2] operates in the animal or human brain,” says Margolzata Kloc, a biochemist at Houston Methodist Medical Research Institute who was not included in the research study. “This can be very difficult due to the fact that TNTs are ephemeral structures and catching them in action can be difficult.”Studying TNTs in human beings requires difficult-to-find, premium post-mortem tissue, which then requires to be imaged at super-high resolution. And given that TNTs are made from simply actin, there are very couple of biomarkers for these tiny structures, making them hard to study and identify from other actin-based protrusions. As a result, TNT-mediated viral infection in vivo simply “isnt well documented,” explains Tiwari. The just in vivo research studies including TNTs Tiwari knows have taken place in the eye.Nath also explains that it remains unclear whether viral entry to the brain is really a vital part of COVID-19 pathology. The infection is seen in brain tissues, it may not be accountable for the neurological signs of COVID-19, given that the quantities seen in neurological samples are low compared to whats seen in lung tissues. “That percentage of virus can not discuss the pathology,” he says.Still, Zurzolo and coworkers speculate that if SARS-CoV-2 does utilize nanotubes to make its way to the brain or elsewise, obstructing TNT formation may be a way to stop the infections early spread and reduce infection seriousness overall. “We certainly require to stop the spread of infection at first,” Zurzolo states, in order to avoid it from creating chaos throughout the body. Like this article? You may also enjoy our Cell & & Molecular Biology newsletter, which is filled with stories like it. You can register for complimentary here.
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 contaminated people post-mortem.”See “Cancer Cell Nanotubes Hijack Mitochondria from Immune Sentinels”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 theyre low on oxygen or during infection. From previous work, Pasteur Institute cell biologist Chiara Zurzolo knew that some viruses use nanotubes to spread out from cell to cell. “It spreads out really quickly throughout the brain and we believe this is a possible system” of how it does so.To test this line of thinking, the scientists cultured Vero E6 cells, which design the cells that line our skin, organs, and blood vessels– and reveal angiotensin-2 converting enzyme (ACE2). The researchers considered these findings strong proof that the TNTs were acting as avenues for viral transmission, likely permitting the virus to get and bypass the blood-brain barrier into the brain.However, Tiwari points out that while the study did show a potential method that neurons could be contaminated, the researchers didnt show evidence that ACE2-positive cells could infect the types of epithelial cells that make up the blood-brain barrier.
