Studies Identify Cell Types Targeted by SARS-CoV-2

Studies Identify Cell Types Targeted by SARS-CoV-2

Two new studies have been published in the past few days that shed light on how SARS-CoV-2 spreads and enters the body and identifies the specific cell types that the virus attacks. While there are similarities between SARS-CoV-2 and SARS-CoV, the exact method of infection with the 2019 Novel Coronavirus was not well understood.

Previous research showed the virus infects cells in the nose and throat; however, nasal and throat swabs taken from patients with symptomatic and asymptomatic COVID-19 show the virus is present in much higher concentrations in nasal cells, which suggests that the infection may start in the nose.

The first study was conducted by an international team of researchers from the Wellcome Sanger Institute in the UK, University Medical Centre Groningen in the Netherlands, and the University Cote d’Azur and CNRS in France. The researchers confirmed that SARS-CoV-2 gains entry into cells by binding to cell surface angiotensin-converting enzyme 2 (ACE2) receptors, similar to other coronaviruses. They showed that SARS-CoV-2 uses its spike protein to bind to the receptor along and also requires an enzyme called TMPRSS2 to activate the protein. Both molecules are required to gain access to the cells.

The study was conducted using single cell RNA sequencing data from tissue samples taken from healthy patients to identify which tissues had both ACE2 and TMPRSS2. They found that in addition to cells in the nose, throat and lungs, the two proteins were also present in cells in the eye and the gut. Since the virus could enter all of these cell types, it helps explain the high level of efficiency of SARS-CoV-2 transmission. The researchers found that the two genes that code for the proteins are highly expressed in goblet and ciliated cells in the nose, suggesting that those cells are the primary way that the virus enters the body and also helping to explain the high level of transmission.

“While there are many factors that contribute to virus transmissibility, our findings are consistent with the rapid infection rates of the virus seen so far. The location of these cells on the surface of the inside of the nose makes them highly accessible to the virus, and also may assist with transmission to other people,” said Martijn Nawijn, PhD, associate professor at the University Medical Center Groningen in the Netherlands.

“This information can be used to better understand how coronavirus spreads. Knowing which exact cell types are important for virus transmission also provides a basis for developing potential treatments to reduce the spread of the virus,” said senior author, Sarah Teichmann, PhD, of the Wellcome Trust Sanger Institute.

A separate study, conducted by researchers at MIT and Harvard University, mirrored the results of the first study but also produced one surprising finding. The expression of the gene for ACE2 correlated with the activation of genes coding for interferon, which is a protein produced by the body in response to viral infection that disrupts viral replication and activates immune cells. While the role of interferon in COVID-19 is not understood, the researchers suggest “SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.”

You can read more about the first study in the paper – SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes – which was published in the journal Nature Medicine (DOI: 10.1038/s41591-020-0868-6) and the second study  – SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues – which was published in the journal Cell. DOI 10.1016/j.cell.2020.04.035.

Image Source: Image Source: CDC/ Alissa Eckert, MS; Dan Higgins, MAM

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