The role of CMKLR1 in lymphocyte activation and localization within the CNS during West Nile Virus Encephalitis

Continued West Nile virus (WNV) outbreaks causing neuroinvasive disease in the US highlight the urgent need to decipher CNS viral control mechanisms. DCs are pivotal in recruiting and reactivating CNS-infiltrating lymphocytes for viral clearance. However, the molecular mechanisms that regulate DC recruitment and activation remain unknown. In CNS-related autoimmune disorders, CMKLR1, a chemokine receptor expressed by a DC subset, aids their recruitment and activation via its ligand, chemerin. To investigate the role of CMKLR1 during WNND, we infected WT and CMKLR1-/- mice with WNV. CMKLR1^-/- mice exhibited a slight increase in mortality but elevated clinical scores accompanied by increased CNS viral loads compared to WT. We hypothesize that CMKLR1 restricts WNV neuropathogenesis by regulating the activation and localization of antiviral T cells within the CNS during WNV encephalitis. Determining the role of CMKLR1 in effector T cell activation and migration may provide insights into local molecular mechanisms controlling lymphocyte function and fate within the CNS during WNV.