When most people think about viral infections, they think in terms of immediate outcomes: you get sick and then you recover. But a growing number of researchers at the University of Louisville are asking different and more complex questions, like what happens to the brain long after an infection is gone? 

Faculty in the Department of Microbiology and Immunology’s virology group are exploring how viral infections may reshape brain health over time, potentially influencing aging, neurodegeneration and susceptibility to diseases like Alzheimer's. This work represents a new frontier in medicine, one that shifts the focus from acute illnesses to lifelong neurological consequences. 

“Historically, infectious disease research has focused on survival and acute outcomes,” said Kevin Sokoloski, associate professor of microbiology and immunology. “But for many viruses, especially those that affect the brain, we simply don’t know what the long-term consequences are, even in those people who never showed obvious [neurological] symptoms.” 

Neuroinflammation, the immune response within the brain, is a natural and often necessary process. But unlike inflammation in other areas of the body, the brain does not regenerate easily. The damage caused by neuroinflammation can be permanent and even subtle changes may leave lasting effects. 

The group’s NIH-funded research is examining how viral infections disrupt inflammatory signaling in the brain and whether those disruptions resolve or leave behind a kind of biological “scar.” 

Several NIH awards are supporting this work, including two major R01 grants and multiple COBRE-funded projects. Each project helps to bridge basic sciences and future clinical application. 

“If you cut your hand, it heals, but you’re left with a scar,” Sokoloski explained. “And the idea is, do we see that in the brain after an infection as well? Right now, clinical care prioritizes getting patients through their acute illness and that is absolutely necessary. But, if we can understand the long-term impacts of infection, we may be able to tailor treatments in ways that protect brain health decades down the line.” 

One of the most exciting ideas emerging from the group’s work is that viruses are not universally harmful. In some cases, past viral infections may even influence future health in unexpected ways.  

“There’s growing evidence that certain viral exposures can alter immune responses in ways that affect susceptibility to other diseases,” Sokoloski said. “That challenges the idea that viruses are only bad.” 

This concept is perhaps most striking in research using modified viruses as therapeutic tools. Sharmila Nair, assistant professor of microbiology and immunology, has been looking specifically at how the Zika virus leverages the virus’s natural ability to target stem cells and repurposing it to attack glioblastoma cells that drive tumor recurrence. 

“It’s a powerful example of how understanding viruses at a fundamental level allows us to turn them into tools for good,” Sokoloski said. 

The collaborative research environment at UofL helps fuel these discussions, leading to complex discoveries. From shared core facilities and data science expertise to institutional investment and support from partners like the Jewish Heritage Fund for Excellence, the university has created the infrastructure needed to pursue cutting-edge research. 

“Good science depends on asking the right questions and being willing to admit you don’t already know the answer,” Sokoloski said. “The collaborative culture here allows us to do exactly that.” 

Department chair, HarbibabuBodduluri, noted that virology research has grown dramatically over the past decade, with millions in new funding and a critical mass of investigators now in place. “This is an exciting moment,” he said. “We’re now positioned to answer questions that weren’t even possible to ask a few years ago.” 

As the recent years have shown, new viral threats can emergequickly, and their long-term effects may not be immediatelyapparent. The research underway at UofL aims to ensure that when those questions arise, science is ready with answers. 

“The solutions of tomorrow are built on the research we do today,” Sokoloski said. “By understanding how infections interact with the brain over a lifetime, we can be better prepared for future public health challenges and, potentially, change how we think about brain health altogether.”