Summary: Researchers have identified specific types of cells that appear to be the targets of the SARS-Cov-2 coronavirus that is causing the Covid-19 pandemic.<\/p>\n\n\n\n Using existing data on the RNA found in different types of cells, the\n researchers were able to search for cells that express the two proteins\n that help the SARS-CoV-2 virus enter human cells. They found subsets of\n cells in the lung, the nasal passages, and the intestine that express \nRNA for both of these proteins much more than other cells.<\/p>\n\n\n\n The researchers hope that their findings will help guide scientists \nwho are working on developing new drug treatments or testing existing \ndrugs that could be repurposed for treating Covid-19.<\/p>\n\n\n\n “Our goal is to get information out to the community and to share \ndata as soon as is humanly possible, so that we can help accelerate \nongoing efforts in the scientific and medical communities,” says Alex K.\n Shalek, the Pfizer-Laubach Career Development Associate Professor of \nChemistry, a core member of MIT’s Institute for Medical Engineering and \nScience (IMES), an extramural member of the Koch Institute for \nIntegrative Cancer Research, an associate member of the Ragon Institute,\n and an institute member at the Broad Institute.<\/p>\n\n\n\n Shalek and Jose Ordovas-Montanes, a former MIT postdoc who now runs \nhis own lab at Boston Children’s Hospital, are the senior authors of the\n study, which appears today in Cell<\/em>. The paper’s lead authors \nare MIT graduate students Carly Ziegler, Samuel Allon, and Sarah \nNyquist; and Ian Mbano, a researcher at the Africa Health Research \nInstitute in Durban, South Africa.<\/p>\n\n\n\n Digging into data<\/strong><\/p>\n\n\n\n Not long after the SARS-CoV-2 outbreak began, scientists discovered \nthat the viral “spike” protein binds to a receptor on human cells known \nas angiotensin-converting enzyme 2 (ACE2). Another human protein, an \nenzyme called TMPRSS2, helps to activate the coronavirus spike protein, \nto allow for cell entry. The combined binding and activation allows the \nvirus to get into host cells.<\/p>\n\n\n\n “As soon as we realized that the role of these proteins had been \nbiochemically confirmed, we started looking to see where those genes \nwere in our existing datasets,” Ordovas-Montanes says. “We were really \nin a good position to start to investigate which are the cells that this\n virus might actually target.”<\/p>\n\n\n\n Shalek’s lab, and many other labs around the world, have performed \nlarge-scale studies of tens of thousands of human, nonhuman primate, and\n mouse cells, in which they use single-cell RNA sequencing technology to\n determine which genes are turned on in a given cell type. Since last \nyear, Nyquist has been building a database with partners at the Broad \nInstitute to store a huge collection of these datasets in one place, \nallowing researchers to study potential roles for particular cells in a \nvariety of infectious diseases.<\/p>\n\n\n\n Much of the data came from labs that belong to the Human Cell Atlas \nproject, whose goal is to catalog the distinctive patterns of gene \nactivity for every cell type in the human body. The datasets that the \nMIT team used for this study included hundreds of cell types from the \nlungs, nasal passages, and intestine. The researchers chose those organs\n for the Covid-19 study because previous evidence had indicated that the\n virus can infect each of them. They then compared their results to cell\n types from unaffected organs.<\/p>\n\n\n\n “Because we have this incredible repository of information, we were \nable to begin to look at what would be likely target cells for \ninfection,” Shalek says. “Even though these datasets weren’t designed \nspecifically to study Covid, it’s hopefully given us a jump start on \nidentifying some of the things that might be relevant there.”<\/p>\n\n\n\n In the nasal passages, the researchers found that goblet secretory \ncells, which produce mucus, express RNAs for both of the proteins that \nSARS-CoV-2 uses to infect cells. In the lungs, they found the RNAs for \nthese proteins mainly in cells called type II pneumocytes. These cells \nline the alveoli (air sacs) of the lungs and are responsible for keeping\n them open.<\/p>\n\n\n\n In the intestine, they found that cells called absorptive \nenterocytes, which are responsible for the absorption of some nutrients,\n express the RNAs for these two proteins more than any other intestinal \ncell type.<\/p>\n\n\n\n “This may not be the full story, but it definitely paints a much more\n precise picture than where the field stood before,” Ordovas-Montanes \nsays. “Now we can say with some level of confidence that these receptors\n are expressed on these specific cells in these tissues.”<\/p>\n\n\n\n Fighting infection<\/strong><\/p>\n\n\n\n In their data, the researchers also saw a surprising phenomenon — \nexpression of the ACE2 gene appeared to be correlated with activation of\n genes that are known to be turned on by interferon, a protein that the \nbody produces in response to viral infection. To explore this further, \nthe researchers performed new experiments in which they treated cells \nthat line the airway with interferon, and they discovered that the \ntreatment did indeed turn on the ACE2 gene.<\/p>\n\n\n\n Interferon helps to fight off infection by interfering with viral \nreplication and helping to activate immune cells. It also turns on a \ndistinctive set of genes that help cells fight off infection. Previous \nstudies have suggested that ACE2 plays a role in helping lung cells to \ntolerate damage, but this is the first time that ACE2 has been connected\n with the interferon response.<\/p>\n\n\n\n The finding suggests that coronaviruses may have evolved to take \nadvantage of host cells’ natural defenses, hijacking some proteins for \ntheir own use.<\/p>\n\n\n\n “This isn’t the only example of that,” Ordovas-Montanes says. “There \nare other examples of coronaviruses and other viruses that actually \ntarget interferon-stimulated genes as ways of getting into cells. In a \nway, it’s the most reliable response of the host.”<\/p>\n\n\n\n Because interferon has so many beneficial effects against viral \ninfection, it is sometimes used to treat infections such as hepatitis B \nand hepatitis C. The findings of the MIT team suggest that interferon’s \npotential role in fighting Covid-19 may be complex. On one hand, it can \nstimulate genes that fight off infection or help cells survive damage, \nbut on the other hand, it may provide extra targets that help the virus \ninfect more cells.<\/p>\n\n\n\n “It’s hard to make any broad conclusions about the role of interferon\n against this virus. The only way we’ll begin to understand that is \nthrough carefully controlled clinical trials,” Shalek says. “What we are\n trying to do is put information out there, because there are so many \nrapid clinical responses that people are making. We’re trying to make \nthem aware of things that might be relevant.”<\/p>\n\n\n\n Shalek now hopes to work with collaborators to profile tissue models \nthat incorporate the cells identified in this study. Such models could \nbe used to test existing antiviral drugs and predict how they might \naffect SARS-CoV-2 infection.<\/p>\n\n\n\n The MIT team and their collaborators have made all the data they used\n in this study available to other labs who want to use it. Much of the \ndata used in this study was generated in collaboration with researchers \naround the world, who were very willing to share it, Shalek says.<\/p>\n\n\n\n “There’s been an incredible outpouring of information from the \nscientific community with a number of different parties interested in \ncontributing to the battle against Covid in any way possible,” he says. \n“It’s been incredible to see a large number of labs from around the \nworld come together to try and collaboratively tackle this.”<\/p>\n\n\n\n The research was funded by the Searle Scholars Program, the Beckman Young Investigator Program, the Pew-Stewart Scholars Program for Cancer Research, a Sloan Fellowship in Chemistry, the National Institutes of Health, the Aeras Foundation, the Bill and Melinda Gates Foundation, the Richard and Susan Smith Family Foundation, the National Institute of General Medical Sciences, the UMass Center for Clinical and Translational Science Project Pilot Program, and the Office of the Assistant Secretary of Defense for Health Affairs.<\/p>\n\n\n\n Story Source:<\/strong><\/p>\n\n\n\n Materials<\/a> provided by Massachusetts Institute of Technology<\/strong><\/a>. Original written by Anne Trafton. Note: Content may be edited for style and length.<\/em><\/p>\n\n\n\n www.sciencedaily.com<\/a><\/p>\n\n\n\n Journal Reference<\/strong>:<\/p>\n\n\n\n![\"\"](\"https:\/\/www.potentialloops.org\/wp-content\/uploads\/2020\/04\/95d3056d580c43bdb53c4f328155a590_18.jpg\")
Researchers at MIT; the Ragon Institute of MGH, MIT, and Harvard; and the Broad Institute of MIT and Harvard; along with colleagues from around the world have identified specific types of cells that appear to be targets of the coronavirus that is causing the Covid-19 pandemic. <\/h4>\n\n\n\n
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