For many patients, recovery from a viral infection marks the end of illness. The fever fades or the symptoms improve, and life returns normal. But emerging research at USF Health suggests that with some viruses, especially as people age, the most serious effects may surface years later, quietly unfolding in the brain.
Bob Gallo and Eleni Markoutsa
Researchers at the 鈥 founded and directed by renowned scientist Robert C. Gallo, MD 鈥 are investigating how viral infections may leave behind lasting changes in the brain that accelerate aging, fuel inflammation and increase vulnerability to neurodegenerative diseases such as Alzheimer鈥檚.
The effort is led by , an assistant professor of internal medicine and head of ITVI鈥檚 Role of Viral Infections in Neurodegenerative Disease Unit.
Her work focuses on a pressing question: If viral infections do accelerate brain aging, can scientists intervene before long-term damage occurs?
Treating complexity, not single targets
Neurodegenerative diseases such as Alzheimer鈥檚 rarely have a singular cause. Instead, they often develop through a complicated mix of aging, genetics, inflammation and environmental factors, including viral infections.
That complexity is one reason these diseases are so difficult to treat. Traditional drug development, often focused on single targets, has struggled to address the multiple damaging processes happening at once.
Dr. Markoutsa approaches the problem differently, looking for ways to act on several disease mechanisms simultaneously.
Her research focuses on discovering new molecular targets in neurodegenerative diseases and designing advanced nanoparticles capable of crossing the blood鈥揵rain barrier to deliver more precise therapies.
鈥淣anotechnology allows us to design therapies that act on multiple disease mechanisms at once,鈥 Markoutsa said. 鈥淲e believe this multifaceted approach is essential for neurodegenerative diseases, where the complexity of disease progression cannot be attributed to a single pathway.鈥
From immune signaling to brain-directed therapies
Markoutsa鈥檚 path to this work began with research into the immune system and how the body responds to disease.
Markoutsa with students, preparing nanoparticles
Early studies examining innate immune activation revealed how shared metabolic signaling pathways regulate inflammation. Those insights later informed her approach to nanodrug delivery.
Through international collaborations focused on Alzheimer鈥檚 disease, she helped develop nanosystems designed to target buildup of beta-amyloid in the brain, a protein closely associated with Alzheimer鈥檚 disease. She later advanced drug-delivery platforms capable of transporting therapies across the blood-brain barrier and delivering them directly to brain tissue.
That work helped lay the foundation for her current research into nanoparticles that can respond to disease signals and deliver therapies in more precise and effective ways. Her lab has also explored nanotechnology-based approaches for treating brain cancers, expanding the potential of precision drug delivery in some of the body鈥檚 most difficult-to-reach areas.
COVID-19, cellular aging and Alzheimer鈥檚 risk
The COVID-19 pandemic added new urgency to Markoutsa鈥檚 research.
At ITVI, she investigates how respiratory viral infections affect the brain during acute illness and long after the initial infection has passed. Her work includes strategies targeting RSV and SARS-CoV-2, as well as extracellular vesicles, tiny particles naturally released by cells that act like biological messengers.
Markoutsa analyzing cellular senescence markers in brain's impacted by Sars-Cov-2
Markoutsa has shown that when stem cells are exposed to inflammation, they release extracellular vesicles with enhanced protective effects. These vesicles carry small molecular signals that can help quiet harmful inflammatory pathways in the body. , those vesicles have shown promise in reducing neuroinflammation, amyloid buildup and damage to nerve fibers.
Today, Markoutsa leads National Institutes of Health-funded research investigating how cellular aging caused by SARS-CoV-2 may accelerate the onset of Alzheimer鈥檚 disease.
鈥淥ur findings show that SARS-CoV-2 increases the burden of senescent cells in the aging brain,鈥 she said. 鈥淭hese cells secrete inflammatory factors that can propagate damage and accelerate pathways linked to Alzheimer鈥檚 disease.鈥
The implications are significant: severe viral infections, particularly COVID-19, may trigger premature cellular aging, increasing the risk of neurodegenerative diseases, even in individuals without a known predisposition. For those already at higher risk, such infections may further accelerate disease progression.
Redefining recovery
Markoutsa鈥檚 work is part of a growing effort at the USF Health Institute for Translation Virology and Innovation to better understand the long-term effects of viral infection and to develop therapies that can move more quickly from the laboratory to patient care.
In addition to serving as principal investigator on an NIH R01, she is a co-investigator on NIH- and Veteran Affairs-funded projects addressing lupus nephritis and the
For Gallo 鈥 who in addition to leading the institute serves as the James P. Cullison Professor of Medicine in the Division of Infectious Disease at USF Health and chair of the scientific leadership board of the Global Virus Network 鈥 Markoutsa鈥檚 research captures a shift in how medicine must think about viruses: not only as acute short-term threats, but as long-term drivers of chronic disease.
鈥淭he future of medicine depends on understanding how infections intersect with aging and chronic disease,鈥 he said. 鈥淭his kind of translational research is essential if we want to reduce the long-term burden of neurodegenerative illness.鈥
As scientists continue to uncover the hidden aftereffects of viral infection, research like this is reshaping how medicine defines recovery and what it means to truly heal.