New research utilizing human-induced pluripotent stem cell-derived skin organoids (hiPSC-SOs) provides groundbreaking insights on the infection pathways of Enterovirus A71 (EV-A71), highlighting its potential threat to children's health.
EV-A71 is known for causing severe health issues, primarily affecting young children, leading to illnesses like hand, foot, and mouth disease. While the virus is typically transmitted through fecal-oral routes, recent findings suggest direct skin contact may also play a significant role.
With no specific antiviral treatments currently available for EV-A71, there is an urgent need for innovative research strategies. Researchers at the Peking Union Medical College Hospital have paved the way by developing hiPSC-SOs as effective models for studying EV-A71 infections and screening potential therapeutics.
These newly developed hiPSC-SOs mimic the architecture and function of human skin, providing a powerful tool for investigating viral infections. The research team observed how various cell types within these organoids, including epidermal, hair follicle, fibroblasts, and nerve cells, interact with the virus. Notably, the study demonstrated how EV-A71 infects these cell types, leading to degradation of extracellular collagen and overall skin damage.
"Using these skin organoids provides insights never before possible," wrote the authors of the article, emphasizing the significance of their findings.
Through single-cell RNA sequencing and proteomics analysis, researchers have detailed the mechanisms of EV-A71 infection, showcasing the complex interplay between the virus and host cells. They identified fibroblasts and epidermal cells as primary targets of the infection. Importantly, they noted alterations within these cells lead to pathological changes associated with skin aging.
Further findings revealed the virus incites significant upregulation of autophagy-related proteins, with HMGB1 identified as a key player. The inhibition of HMGB1 resulted in reduced viral replication. This suggests potential therapeutic targets for managing EV-A71 infections.
Another key discovery was the impact of EV-A71 on progenitor cells within the skin. The research indicated significant overproliferation of NNMT + SFRP1+ progenitor cells following viral infection, driven by disrupted signaling pathways such as Hippo-YAP/TAZ, which is prevalent during cancer progression. This raises concern about the potential link between viral infections and tumorigenesis.
Notably, the authors underscored the findings, stating, "Understanding the mechanisms of EV-A71 infection can steer us toward designing novel therapeutic strategies."
The significance of developing effective antiviral treatments is underscored by recent EV-A71 outbreaks throughout the Asia-Pacific region, stressing the importance of timely intervention. By utilizing hiPSC-SOs, this research opens avenues for future antiviral drug screenings and therapeutic advancement.
Concluding, the research not only highlights the importance of hiPSC-SOs as models for studying viral pathogenesis but also outlines potential directions for addressing public health challenges posed by EV-A71. With pressing needs met by these innovative models, researchers are hopeful for the development of drugs capable of combating this prevalent virus.