Targeting Cellular Pathways to Halt Deadly Rotavirus Infection

Recent research from Washington University School of Medicine in St. Louis has uncovered a promising strategy to combat rotavirus, a leading cause of severe dehydrating diarrhea in infants and young children worldwide. Despite the availability of vaccines, rotavirus continues to pose a significant health threat, particularly in regions with low vaccination coverage, contributing to over 128,500 deaths annually globally. Moreover, declining vaccination rates in the United States have led to increasing cases.

The study focused on how rotavirus infects cells and identified a crucial host enzyme, fatty acid 2-hydroxylase (FA2H), which facilitates the virus's ability to escape from cellular compartments called endosomes. When the virus enters a cell, it becomes trapped inside these endosomes, preventing infection. The research demonstrated that disabling FA2H, using advanced gene editing techniques, caused the virus to remain confined within endosomes, thereby blocking replication.

In genetically modified mice lacking FA2H in intestinal cells, infection symptoms were significantly reduced, confirming the enzyme's role in infection. This approach differs from traditional vaccines by intervening directly in the infection process and potentially offering a broad-spectrum method to prevent similar pathogens relying on the same entry mechanisms.

Furthermore, the study suggests that FA2H is not only involved in rotavirus infection but also plays a role in other pathogens like Junín virus and Shiga toxin, indicating a common "entry code" used by multiple disease-causing agents. Targeting this pathway could lead to new therapeutic options that bolster host defenses against various infectious diseases.

Ding emphasized that this discovery opens the door for developing drugs that inhibit FA2H activity, providing an innovative host-based defense mechanism. Such therapies could complement vaccines, especially for vulnerable populations who remain unvaccinated or are at risk of severe disease.

The findings are published in the Proceedings of the National Academy of Sciences (PNAS), and represent a significant advancement in understanding viral entry mechanisms, offering hope for future treatments that could reduce the global burden of rotavirus and similar infections.

Source: https://medicalxpress.com/news/2025-10-disabling-critical-cellular-pathway-key.html