As obligate intracellular parasites, viruses rely on fine-tuned interactions with their hosts. Nevertheless, host switching is observed for viruses with a high degree of adaptive plasticity and a high mutation rate, such as certain coronaviruses. SARS-CoV-2 spilled over to humans possibly from bats and since this event has adapted to optimize its transmission between humans. However, traditionally, pathogenic viruses are studied in experimental animal models, in which specific virus-host interactions may not be modelled correctly, forcing viruses to adapt and limiting the use of these models. Studying SARS-CoV-2 pathogenesis and biology, as well as identifying potential treatments therefore benefits from the development of in vitro cell culture systems that closely mimic human physiology. We have established human organoid systems of the intestines, airways and alveoli to study the pathogenesis, cell biology and evolution of SARS-CoV-2. Combining these systems with CRISPR/Cas9 gene editing technology allows the identification of realistic antiviral drug targets. In addition, our findings unveil human organoids as powerful tools to phenotype SARS-CoV-2 variants-of-concern and identify correlates of fitness for SARS-CoV-2. Organoids are emerging as versatile tools to study SARS-CoV-2, laying a foundation for future pandemic responses.
Physiology 2021 (2021) Proc Physiol Soc 48, SA39
Research Symposium: Human organoid systems to study the pathogenesis, cell biology and evolution of SARS-CoV-2
Mart Lamers1, Joep Beumer2, 3, Tim Breugem1, Anna Mykytyn1, Maarten Geurts2, 3, Jelte van der Vaart2, 3, Hans Clevers2, 3, Bart Haagmans1
1 Viroscience Department, Erasmus Medical Center, Rotterdam, The Netherlands 2 Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, Utrecht, The Netherlands 3 University Medical Center, Utrecht, The Netherlands
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Where applicable, experiments conform with Society ethical requirements.