Writing in the journal Cell Stem Cell, the researchers detail the mechanisms underlying SARS-CoV-2 infection and the early innate immune response in the lungs.
To date, there have been more than 40 million cases of COVID-19 and almost 1.13 million deaths worldwide. The main target tissues of SARS-CoV-2, the virus that causes COVID-19, especially in patients that develop pneumonia, appear to be alveoli – tiny air sacs in the lungs that take up the oxygen we breathe and exchange it with carbon dioxide to exhale.
To better understand how SARS-CoV-2 infects the lungs and causes disease, a team of scientists from the UK and South Korea turned to organoids – ‘mini-organs’ grown in three dimensions to mimic the behaviour of tissue and organs.
The team used tissue donated to tissue banks at the Royal Papworth Hospital NHS Foundation Trust and Addenbrooke’s Hospital, Cambridge University NHS Foundations Trust, UK, and Seoul National University Hospital to extract a type of lung cell known as human lung alveolar type 2 cells. By reprogramming these cells back to their earlier ‘stem cell’ stage, they were able to grow self-organising alveolar-like 3D structures that mimic the behaviour of key lung tissue.
Dr Joo-Hyeon Lee, co-senior author, and a Group Leader at the Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, said: “We still know surprisingly little about how SARS-CoV-2 infects the lungs and causes disease. Our approach has allowed us to grow 3D models of key lung tissue – in a sense, ‘mini-lungs’ – in the lab and study what happens when they become infected.”
The team infected the organoids with a strain of SARS-CoV-2 taken from a patient in South Korea who was diagnosed with COVID-19 on 26 January 26 2020 after traveling to Wuhan, China. Using a combination of fluorescence imaging and single cell genetic analysis, they were able to study how the cells responded to the virus.
When the 3D models were exposed to SARS-CoV-2, the virus began to replicate rapidly, reaching full cellular infection just six hours after infection. Replication enables the virus to spread throughout the body, infecting other cells and tissue.
Image: Representative image of three-dimensional human lung alveolar organoid showing alveolar stem cell marker, HTII-280 (red) and SARS-CoV-2 entry protein, ACE2 (green).
Credit: Jeonghwan Youk, Taewoo Kim, and Seon Pyo Hong
Reproduced courtesy of the University of Cambridge