Defining the functional role of chemokines/chemokine receptors following JHMV-induced neurologic disease:
My laboratory has a long-standing interest in understanding events that initiate and maintain inflammation within the CNS in response to JHMV infection. To this end, we’ve focused upon determining the functional significance of chemokines and chemokine receptors in both host defense as well as disease development in JHMV-infected animals. Indeed, we were among the first laboratories to show that blocking chemokine function via either antibody neutralization or genetic silencing resulted in increased mortality accompanied by reduced immune cell infiltration into the CNS in response to acute JHMV-induced disease. Moreover, we demonstrated that targeting selected chemokines in mice persistently infected with JHMV attenuated the severity of neuroinflammation and demyelination resulting in improved motor skills associated with increased remyelination. Subsequently, we have shown that unique chemokine/chemokine receptor signaling pathways are critical for interrelated events required for optimal host defense following viral infection including recruiting myeloid cells to the CNS that contribute to increasing the permeability of the blood-brain-barrier (BBB) and linking innate and adaptive immune responses. More recently, we have focused on how chemokines/chemokine receptors influence neutrophil accumulation within the CNS of JHMV mice as well as regulating the biology of oligodendroglia in terms of maturing into myelin-producing oligodendrocytes, and influencing remyelination. This work is funded by NIH grant R01 NS041249 and National MS Society Collaborative Center Grant CA-1607-25040.