When Gaby Madrigal peered through a powerful microscope at the University of Vermont, she expected to see immune cells destroying viruses. Instead, she watched dengue slip right inside and set up camp.
Madrigal, a graduate student at UVM's Cellular, Molecular, and Biomedical Science program, and her colleagues discovered that dengue virus can infect and replicate inside memory B cells — the very immune cells that normally help protect us from disease. The finding, published July 20 in the Journal of Virology, could open doors to entirely new treatments for a disease that quietly threatens billions of people worldwide.
Dengue spreads through the bite of tropical mosquitoes and causes high fevers, severe headaches, and debilitating bone and muscle pain. In the worst cases, it damages blood vessels and can cause dangerous drops in blood pressure. Four different strains of dengue circulate globally, infecting an estimated 100 million people each year. More than 4 billion people live in regions where the mosquitoes that carry it are present, including parts of the southern United States.
Scientists have known for decades that catching dengue once can sometimes make a second infection worse. During a first infection, the body makes proteins called antibodies that should fight the virus. But when someone catches a different dengue strain later, those same antibodies can accidentally help the new virus enter certain immune cells — a phenomenon called antibody-dependent enhancement. The new research reveals another troubling pathway the virus uses.
The team, led by Sean Diehl, Ph.D. at the University of Vermont and Adam Waickman, Ph.D. at Upstate Medical University in Syracuse, New York, showed that dengue can infect B cells through a surface molecule called the B cell receptor. They named this process "B cell receptor-dependent enhancement," or BDE. Using advanced microscopy techniques developed with Menelaos Symeonides, Ph.D., the researchers watched dengue enter these cells and identified — spots where the infection process might be interrupted.
What makes this especially concerning is that memory B cells stick around for years after an initial infection, in the body ready to respond. The study showed that all four dengue types can infect these cells, meaning they could serve as hidden reservoirs where the virus persists.
The discovery comes with a potential silver lining. Several drugs that target B cells already exist — they're approved for treating certain cancers and autoimmune diseases. Since the researchers identified the specific molecular pathways the virus uses to infect these cells, those existing medications might someday be adapted to fight dengue.
"It's a high bar to show something genuinely new in dengue research," Diehl said. He called the work "high-quality data produced by trainees who rose to the occasion." Chad Gebo, a staff scientist at Upstate and recent Ph.D. graduate, co-led the study with Madrigal.
No approved dengue-specific drugs currently exist, and vaccines have faced challenges with broad effectiveness. The team's findings offer a fresh avenue worth exploring — one that starts not with a new compound, but with understanding how an old enemy finds new ways to survive.