Project Type(s):
Basic Science

Infection by West Nile Virus can lead to encephalitis, or harmful inflammation of the brain. The immune system is critical for controlling viral replication and spread early in West Nile Virus infection, but persistent immune activation causes encephalitis that can result in brain damage even after the virus has been cleared. Recent pharmacologic advances have produced drugs that modulate the body’s immune response and can control inflammation, but these drugs have not yet been tested in conditions of viral encephalitis. In order for patients to benefit from these therapies, clinicians need tools that help identify when excessive immune activity is causing encephalitis.

The key innovation of this project is the combination of noninvasive imaging with novel immune modulating drugs to improve the diagnosis and treatment of encephalitis. Our central hypothesis is that specialized immune cells known as macrophages are key drivers of encephalitis in West Nile Virus infection, and that preventing their activation will preserve memory and other cognitive functions. Our studies will explore and develop noninvasive positron emission tomography (PET) imaging as a tool for diagnosing brain inflammation. We will test our hypothesis utilizing West Nile Virus infection of mice, which captures the key elements of human disease including encephalitis. This model allows us to evaluate existing diagnostic and therapeutic tools currently used in humans for other purposes, from which we will define new clinical applications. We will thus be poised to translate our findings to human studies defining and treating viral encephalitis.

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