George Mason researchers assess nicotine’s long-term health impact in those with HIV-related brain disease in NIH study

A new $3.8 million grant from the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH), brings together two George Mason University researchers from different scientific disciplines to tackle an emerging health challenge at the intersection of HIV and nicotine use.

The five-year award supports the project "Impacts of HIV and Nicotine on T Cell Neuroinvasion and CNS Reservoir Seeding," co-led by Yuntao Wu, professor and co-director in George Mason's Center for Infectious Disease Research, and Nadine Kabbani, professor and associate chair for research in George Mason's Interdisciplinary Program in Neuroscience.

The researchers are investigating how chronic nicotine use may influence the entry of HIV-infected immune cells into the brain. Although modern antiretroviral therapy has transformed HIV into a manageable chronic condition, allowing people with HIV to live longer and healthier lives, cognitive and neurological complications remain disproportionately common and may become increasingly important as this population ages.

"NeuroAIDS is an established field investigating the long-term neurological and cognitive consequences of HIV infection," said Kabbani. "Even when antiviral medications successfully suppress viral production in immune cells, HIV-related complications persist in infected individuals. We want to understand whether nicotine use, which is high amongst HIV infected individuals, may be contributing to the virus's ability to enter the brain and worsen those outcomes."

The project combines Kabbani's extensive expertise in nicotine and neuroimmune signaling with Wu's more than two decades of HIV/AIDS research leadership at George Mason.

"This grant is an example of how our collaborative research can bring new knowledge, new expertise, and new technologies into HIV/AIDS research," said Wu, who established the university's HIV research program. "By combining strengths across disciplines, we can explore questions that neither lab could answer alone."

The multidisciplinary College of Science-based team will begin by studying human immune cells in laboratory models to understand how nicotine affects HIV infection and the biological pathways that allow infected T cells to cross into the central nervous system. Researchers will then apply that knowledge to advanced "humanized" mouse models, in which human immune cells infected with HIV are introduced into mice to study how the virus behaves in a living system.

The group is guided by a central hypothesis that chronic nicotine use can alter both immune cells and the blood-brain barrier in ways that may allow HIV-infected cells greater access to the brain.

The work addresses an important public health concern. "People with HIV are living longer, which is wonderful," said Wu. "But now we need better science to improve quality of life. Many patients experience neurological complications despite treatment. We believe nicotine may be one factor that worsens those outcomes, and we need to understand why."

The project will also create extensive opportunities for student researchers. The combined George Mason team of approximately 10 to 15 researchers includes PhD students, technicians, and postdoctoral fellows who meet regularly across the university's Fairfax and Science and Technology campuses.

Neuroscience doctoral student Natalie Erickson will gain experience in HIV research, while students from Wu's laboratory, including Presidential Scholar Elizabeth Spencer, will also participate in the project.

Student training remains a key outcome of the grant. "The students are learning cutting-edge science while contributing to research that has real potential to improve the lives of people living with HIV," Wu said.

The study also builds on a longstanding partnership between College of Science researchers and the university community. Many of Wu's HIV studies rely on donated blood samples from George Mason volunteers, allowing researchers to create laboratory models using healthy human immune cells.

Kabbani suggests that the project embodies the promise of interdisciplinary discovery. "The brain and immune system are deeply connected," she said. "Understanding how viruses, immune cells, and drugs of abuse like nicotine interact gives us a new opportunity to understand both brain health and disease. That intersection between neuroscience and virology is where some of the most exciting discoveries are waiting to happen."

The project, which began this summer, runs through May 31, 2031.