"Viral Encephalitis: Phenotyping Leukocyte Infiltration
into the Central Nervous System as a
Result of Rift Valley Fever Virus Infection"
Abstract: Rift Valley Fever Virus (RVFV) is a vector-borne infection endemic to the Horne of Africa; However, 2001 outbreaks in the Arabian Peninsula demonstrate its expanding range. Humans can develop encephalitis as a result of RVFV infection. Our lab uses an immunocompetent Lewis rat model to study neuropathogenesis of RVFV, which uniformly develop lethal encephalitis within 7 – 8 days after aerosol exposure. Lewis rats infected subcutaneously do not develop apparent disease. The goal of this study is to characterize the phenotypes, timing, and extent of immune cell infiltrate into the CNS of RVFV-infected Lewis rats. Lewis rats were infected with RVFV ZH501 by aerosol or subcutaneous routes, and subsequently serial sacrificed between 1 and 7 days post infection. Rat immune cells were isolated from brains via percoll gradients, were stained with the appropriate antibodies, run on a BD LSRII flow cytometer, and analyzed with FlowJo 7.6.5.
In aerosol infected rats, the leukocyte infiltrate 5 days post infection and later, consisted of primarily neutrophils, corresponding to the clinical window. Rats infected subcutaneously had detectable infiltrate, despite no apparent disease, which primarily consisted of phenotypic CD4+ T cells. These findings suggest that aerosol infected rats mainly exhibit innate leukocyte infiltration to the brain while subcutaneous have limited leukocyte infiltration and display a stronger adaptive immune response. The relative contributions of viral cytopathology versus immunopathology remain to be determined, but this study represent the first attempt to characterize the leukocytic component of RVFV infection.