Researchers at the University of Vermont Robert Larner, M.D. College of Medicine and Upstate Medical University in Syracuse, New York, announced on July 27 that dengue virus can infect and replicate inside memory B cells. These immune cells are traditionally understood to help protect the body from infection. The findings were published July 20 in the Journal of Virology.
The study was conducted by teams led by Sean Diehl, Ph.D., professor of Microbiology and Molecular Genetics at the University of Vermont, and Adam Waickman, Ph.D., associate professor of Microbiology and Immunology at Upstate Medical University. The researchers found that all four types of dengue viruses can enter memory B cells through a process involving the B cell receptor on the cell surface. Co-led by graduate student Gaby Madrigal and staff scientist Chad Gebo, the team demonstrated that these infected memory B cells could produce infectious virus.
Dengue is transmitted by tropical mosquitoes and affects an estimated 100 million people each year worldwide. More than four billion people live in regions where dengue-carrying mosquitoes are present. Symptoms range from high fever to severe headaches and muscle pain; severe cases may involve complications such as damage to blood vessels or dangerously low blood pressure.
Scientists have previously identified antibody-dependent enhancement (ADE), where antibodies from a first infection bind but do not neutralize a second strain, allowing easier entry into immune cells. Earlier work from Diehl's and Waickman's laboratories suggested another pathway: B cell receptor-dependent enhancement (BDE), where dengue enters B cells directly via their receptors.
In this new study, advanced microscopy techniques allowed visualization of how dengue enters memory B cells. Researchers identified potential vulnerabilities in molecular signaling pathways required for infection through collaboration with Menelaos Symeonides, Ph.D., assistant professor at UVM.
"This work challenges existing assumptions about how dengue interacts with the immune system," said Diehl. "By revealing a previously unrecognized route of infection, it opens new avenues for understanding dengue disease and developing interventions to prevent or treat it."
