Lymphocyte Brain Entry May Help in Encephalitis
Using chemokine-receptor antagonist improved survival in mouse model of West Nile virus
WEDNESDAY, Aug. 6 (HealthDay News) -- Inhibiting a chemokine receptor at the blood-brain barrier during West Nile virus infection in mice improved T-cell infiltration in the brain and improved survival, according to research published online Aug. 4 in the Proceedings of the National Academy of Sciences Early Edition.
Erin E. McCandless, of the Washington University School of Medicine in St. Louis, and colleagues experimented with a mouse model of acute West Nile virus infection. They treated mice with an antagonist of CXCR4, a receptor on leukocytes that engages the chemokine CXCL12, which is expressed in central nervous system endothelial cells. Administering the antagonist starting at the time of infection increased survival to 50 percent compared to infected mice that only received vehicle.
CXCR4 antagonism may improve T-cell migration into the brain, allowing better interaction between virus-specific CD8+ T cells with infected target cells, speeding viral clearance, the authors write. In addition, at eight days after infection, when treated mice were recovering and control mice were dying, control mice showed more astrocyte activation, suggesting that CXCR4 antagonism may minimize harmful immune activation during viral encephalitis.
"Based on our studies, CXCR4 antagonists may be expected to expedite viral clearance in acute viral encephalitides that require influx of protective lymphocytes. Thus, regulation of leukocyte infiltration may be a therapeutic strategy for control of central nervous system viruses, many of which lack specific treatments," the authors write. "Immunotherapy with CXCR4 antagonists alone or in combination with antiviral modalities might enhance clearance within the central nervous system in potentially fatal viral infections."