Coronavirus Lab
Duke-NUS Medical School
Emerging Infectious Diseases Programme
The interface of
virology and organoid biology
News
February 2024: New study out! In this extensive review, Drs. Mart Lamers and Julie Chu highlight the key insights that have been contributed by organoid models to virus research. Organoids in virology.
August 2023: New study out! Mykytyn, A.Z., Breugem, T.I., Geurts, M.H., Beumer, J., Schipper, D., van Acker, R., van den Doel, P.B., van Royen, M.E., Zhang, J., Clevers, H., Haagmans, B.L.*, and Lamers, M.M.* (2023). SARS-CoV-2 Omicron entry is type II transmembrane serine protease-mediated in human airway and intestinal organoid models. Aug 9, 2023. J Virol, e0085123,10.1128/jvi.00851-23
We need to prepare for the next pandemic
The planet’s current changes in human and domestic animal population size, urbanization, global connectivity, climate, wildlife trade, ecosystem health and land use, guarantee that humanity will face new, previously unrecognized animal viruses that can infect humans (zoonotic viruses) in the next decades. Among zoonotic viruses, coronaviruses pose a high risk to global health due to their abundance and diversity in wildlife and proven ability to adapt to infect and spread between humans.
The problem
Traditionally, virology has relied mainly on transformed/cancerous cell lines and animal models to study viral biology, with important caveats. Cell lines have drifted extensively from their natural in-vivo counterparts and often have defects in cellular innate immunity, allowing unbridled viral replication. Animal models are important tools to study viral pathogenesis, immune responses, and the effect of interventions. However, they are labor-intensive and expensive, and often recapitulate only specific aspects of a particular human disease. Furthermore, both cell lines and animal models present viral target cells that are not necessarily representative of the target cells in humans. For example, the rapid adaptation of SARS-CoV-2 to specific cell lines and animals indicates initial mismatch in virus–host interactions and rapid evolution, which could result in the incorrect modelling of defining features of SARS-CoV-2 biology in humans.
The solution: organoids
Organoids are three-dimensional (3D) in-vitro structures grown from stem cells, which consist of organ-specific cell types that self-organise according to intrinsic developmental programmes, resulting in tissue morphology that recapitulates organ architecture with remarkable fidelity. The fact that these tissues can be derived from human cell progenitors and can continue to self-renew in culture has opened many new avenues for experimental biology, in particular when combined with gene editing technology. In the past few years, human organoids have been used to study a wide range of viruses. They have particularly advanced our understanding of SARS-CoV-2 biology, and have laid a foundation to study newly emerging viruses.