How SARS-CoV-2 (COVID-19) Gets into Respiratory Tissue — And How It May Exploit One of Our Anti-Viral Defenses; Interferon Boosts ACE2, Which Is Cell Surface Receptor That COVID-19 Binds To

What makes SARS-CoV-2, the virus behind COVID-19, such a threat? A new study, led by Jose Ordovas-Montanes, PhD at Boston Children's Hospital and Alex K. Shalek, PhD, at MIT, pinpoints the likely cell types the virus infects. Unexpectedly, it also shows that one of the body's main defenses against viral infections may actually help the virus infect those very cells. Findings were published online on April 21, 2020 in Cell ( The peer-reviewed study, published as a preprint, will help focus efforts to understand what SARS-COV-2 does in the body, why some people are more susceptible, and how best to search for treatments, the researchers say. The pre-print is titled “SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene In Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets Across Tissues.” When news broke about a new coronavirus in China, Dr. Ordovas-Montanes and Dr. Shalek had already been studying different cell types from throughout the human respiratory system and intestine. They also had gathered data from primates and mice. In February, they began diving into these data. "We started to look at cells from tissues such as the lining of the nasal cavity, the lungs, and gut, based on reported symptoms and where the virus has been detected," says Dr. Ordovas-Montanes. "We wanted to provide the best information possible across our entire spectrum of research models." Recent research had found that SARS-CoV-2--like the closely related SARS-CoV that caused the SARS pandemic--uses a receptor called ACE2 (angiotensin-converting enzyme 2) to gain entry into human cells, aided by an enzyme called TMPRSS2 (transmembrane serine protease 2). That led Dr. Ordovas-Montanes and Dr. Shalek and colleagues to ask a simple question: which cells in respiratory and intestinal tissue express both ACE2 and TMPRSS2?
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