The Role of Chemokines during Viral Infection of the CNS

Hosking, Martin P.; Lane, Thomas E.

Although early signaling events are clearly important for host defense during viral infection, the infiltration and anti-viral activity of T lymphocytes are requisite for viral clearance and survival. CXCL10, which is prominently expressed within the CNS during many viral infections [1, 17] , functions to attract activated T lymphocytes bearing the receptor CXCR3. Neutralization or genetic silencing of CXCL10 following infection with HSV, JHMV, and WNV dramatically reduces T cell trafficking into the CNS, thus preventing efficient viral control and often resulting in poor resolution [6, 18, 19] . In addition to attracting T lymphocytes, the CXCR3 ligands CXCL10 and CXCL9 also attract natural killer (NK) cells during JHMV infection [20, 21] ; however, their role in viral clearance remains unclear. The macrophage and T lymphocyte chemokine CCL5, or one of its receptors, CCR5, also promotes leukocyte trafficking into the CNS and subsequent viral control during JHMV infection and WNV-induced encephalitis [22, 23] . The clinical relevance of this observation was revealed when homozygosity for the defective human CCR5 allele (CCR5D32) was associated with an increased risk for symptomatic WNV infection [24] . Collectively, these data demonstrated that chemokine expression during viral infection promotes the generation and infiltration of immune effector cells necessary for quelling viral replication ( Figure 1B ).