In an effort to determine the potential for COVID-19 to start in a person’s gut and better understand how human cells respond to SARS-CoV-2, scientists used human gut cells to create organoids – human-derived 3D tissue cultures. cells, which mimic the tissue or organ the cells come from. Their findings, published in the journal Biology of molecular systems, indicate the potential for infection to harbor in a host’s intestines and reveal the intricacies of the immune response to SARS-CoV-2.
“Previous research had shown that SARS-CoV-2 can infect the gut,” says Theodore Alexandrov, who heads one of the two EMBL groups involved. “However, it is not known how the intestinal cells mount their immune response to infection.”
In fact, the researchers were able to determine the type of cell most severely infected with the virus, how infected cells trigger an immune response, and – most interestingly – that SARS-CoV-2 silences the immune response of children. infected cells. These findings may shed light on the pathogenesis of SARS-CoV-2 infection in the gut and indicate why the gut must be considered to fully understand how COVID-19 develops and spreads.
According to Sergio Triana, lead author and doctoral student in EMBL’s Alexandrov team, the researchers observed how infected cells appear to trigger a cascade of events that produce a signaling molecule called interferon.
“Interestingly, although most cells in our mini-intestines have a strong immune response triggered by interferon, cells infected with SARS-CoV-2 did not react in the same way and instead exhibited a strong pro-inflammatory response, ”says Sergio. “This suggests that SARS-CoV-2 interferes with host signaling to disrupt an immune response at the cellular level.”
Coronaviruses, including SARS-CoV-2, cause infection by attaching to specific protein receptors found on the surface of certain types of cells. Among these receptors is the ACE2 protein. Interestingly, the researchers showed that the infection was not explained solely by the presence of ACE2 on the surface of the cells, highlighting our still limited knowledge about COVID-19, even after a year of enormous efforts. research in the world.
As the disease progressed into the organoids, the researchers used single-cell RNA sequencing, which involves several techniques to amplify and detect RNA. Among these single-cell technologies, Targeted Perturb-seq (TAP-seq) provided sensitive detection of SARS-CoV-2 in infected organoids. Lars Steinmetz’s research group at EMBL recently developed TAP-seq, which researchers combined with powerful computational tools, allowing them to detect, quantify and compare the expression of thousands of genes in individual cells to within organoids.
“This finding could offer insight into how SARS-CoV-2 protects the immune system and offer alternative ways to treat it,” Lars says. “Further study can help us understand how the virus develops and the different ways it affects the human immune system.”
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Material provided by European Molecular Biology Laboratory. Original written by Ivy Kupec. Note: Content can be changed for style and length.