IL-1β induces the formation of actin bundles (green) in structures separating cells and preventing them from fusing with each other, which decreases the transmission of SARS-CoV-2 (red) within human lung cells. Image credit: Zheng et al. (CC BY 4.0)
SARS-CoV-2, the agent responsible for COVID-19, has claimed millions of lives across the globe. To better manage this disease and develop new treatments, it is fundamental to understand how the immune system responds to this virus – and, in particular, how it can be thwarted.
Like all viruses, SARS-CoV-2 replicates within host cells and bursts out when it has made more of itself and is ready to infect more tissues. It can also cause neighbouring cells to merge, allowing the virus to replicate and spread without stepping outside. This strategy makes it harder for the immune system to access and deactivate the threat.
A group of molecules called proinflammatory cytokines (such as IL-1β and IL-1α) are released upon SARS-CoV-2 infection. People receiving immunosuppressive therapies, which can reduce proinflammatory cytokine levels to harness inflammatory damage, find it harder to tackle the virus. However, the full role of these molecules in clearing SARS-CoV-2 remains unknown.
To investigate this question, Zheng, Yu, Zhou and Yu et al. developed different experimental models that could examine how proinflammatory cytokines might protect cells from SARS-CoV-2 challenge. The results showed that IL-1β and IL-1α stop the virus from being able to fuse cells together. Further cell studies revealed the underlying mechanism: IL-1β triggers cells to increase the levels of essential components, known as actin bundles, which form the structures that prevent cells from fusing with each other. Experiments in live mice showed that IL-1β treatment significantly prevented SARS-CoV-2 from spreading within the lining of the lungs. Taken together, these findings reveal new insights into how the immune system protects hosts against SARS-CoV-2 infection; further investigation may help identify new treatments for COVID-19.
