West Nile virus (WNV) is an emerging arbovirus that disproportionately causes severe neurological disease in elderly individuals. This dissertation describes the development of a novel aged-mouse model of WNV infection to investigate age-related factors contributing to increased disease susceptibility. Using this model, we demonstrate that aged mice exhibit enhanced susceptibility to WNV encephalitis associated with defects in antigen-specific T cell responses, including impaired production of interferon-γ and granzyme B. We further identify WNV-specific CD4 and CD8 T cell epitopes and characterize functional T cell responses in C57BL/6 mice. These findings advance understanding of immune senescence in WNV infection and support the development of targeted vaccines and therapeutics for the elderly.
