Graduate student California Polytechnic State Univ. Covina, California, United States
Introduction/Rationale: West Nile virus (WNV ) is a neurotropic flavivirus and the leading cause of mosquito-borne viral encephalitis in the United States. Nearly half of WNV survivors experience long-term neurological impairments, highlighting the urgent need to understand better the immune mechanisms that contribute to neuropathology. Microglia, the resident immune cells of the central nervous system (CNS), are key responders to WNV infection. Their activation can be protective or pathological depending on context. Chemokine-like receptor 1 (CMKLR1) is a G protein-coupled receptor implicated in immune cell migration, inflammation, and signaling. CMKLR1 has also been associated with regulation of the purinergic receptor P2RY12, which mediates microglial motility and chemotaxis during CNS injury. We hypothesize that CMKLR1 regulates microglial activation and migration in response to WNV infection and influences disease progression.
Methods: To test this, we are comparing microglial responses in wild-type (WT) and CMKLR1-deficient mice following WNV infection. Using immunohistochemistry, confocal microscopy, and cytokine profiling, we are assessing microglial morphology, activation status, cytokine expression, and localization relative to infected brain regions.
Results: Preliminary findings indicate altered microglial distribution and morphology in CMKLR1-deficient mice compared to wild-type controls. Microglia from CMKLR1-deficient mice exhibited reduced P2RY12 expression suggesting that CMKLR1 plays a critical role in early microglial activation in WNV infection.
Conclusion: These studies aim to clarify the role of CMKLR1 in neuroimmune regulation during viral encephalitis and may identify novel therapeutic targets to mitigate WNV-induced neuroinflammation.
