Chemokine Responses in Virus-Induced Neurologic Disease: Balancing Host Defense and Neuropathology

This chapter focuses on the chemokine response to viral infection of the central nervous system (CNS) with an emphasis on the functional significance of chemokine expression as it relates to both host defense and neuropathology. Available evidence demonstrates clearly that viral infection of the CNS results in a dramatic increase in chemokine gene expression. Moreover, production of chemokines in response to infection is highly focused within areas of viral replication early in the disease process and areas of viral RNA persistence during the chronic stages of disease. Resident glial cells are capable of generating a robust chemokine response following viral infection in the absence of inflammatory cells suggesting that this response may reflect an innate CNS response against viral infection analogous to the response of phagocytic cells in the periphery. Differences in virus and cellular tropism are likely explanations for the slight differences in chemokine profiles and duration of expression observed in the different models. The non-ELR CXC chemokine CXCL10 is often the predominant chemokine expressed early following viral infection suggesting an important role as a sentinel molecule in initiating neuroinflammation. Based on the studies presented in this chapter, it is clear that targeting chemokines during either acute or chronic viral-induced CNS disease may offer exciting new insights into potentially novel interventional mechanisms in treating human neuroinflammatory diseases.