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Chemokines and Clearance of West Nile Virus Infection

  • Chapter
West Nile Encephalitis Virus Infection

Part of the book series: Emerging Infectious Diseases of the 21 Century ((EIDC))

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Abstract

West Nile virus (WNV) is a neurotropic flavivirus that can lead to fatal neuroinvasive infection. Recent studies indicate that innate and adaptive immune responses are critical for clearing infection in the periphery and preventing viral dissemination into the central nervous system (CNS). Clearance of WNV within the CNS compartment, however, specifically requires the infiltration of virus-specific T cells. Chemokines are chemoat-tractant molecules expressed early in the course of WNV infection that participate in leukocyte migration and activation both in the periphery and during CNS dissemination. As WNV leads to predominantly Th1 antiviral immune responses, chemokines that attract these cells might be particularly important in disease progression especially with regard to neuroinvasive disease. In this review, we focus on the role of chemokine members of the CXC or CC subfamilies. Among the CXC chemokines, the non-ELR group comprised of CXCL9–11, attract Th1 cells through the interaction with their receptor, CXCR3. Among the CC subfamily, Th1-associated chemokines include CCL3–5. These chemokines attract cells through an interaction with their receptor, CCR5. Secondary lymphoid and CNS tissue levels of all of these chemokines are elevated during primary infection with WNV, while homeostatic chemokines, including CXCL12 are decreased at the CNS microvasculature during WNV encephalitis. Among the proinflammatory chemokines, CXCL10 is dominantly expressed by WNV-infected neurons. Thus, chemokine gradients tightly regulate T-cell entry into and within the CNS. In the future, manipulation of chemokine receptor activation might be used to control the trafficking of virus-specific T cells and improve viral clearance within the CNS in patients with WNV encephalitis

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Acknowledgments

This work was supported by NIH/NINDS NS045607 and NS052632 and by a grant from the Midwest Regional Center for Excellence in Emerging Infectious Diseases.

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  1. Robyn S. Klein
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Klein, R.S. (2009). Chemokines and Clearance of West Nile Virus Infection. In: West Nile Encephalitis Virus Infection. Emerging Infectious Diseases of the 21st Century. Springer, New York, NY. https://doi.org/10.1007/978-0-387-79840-0_15

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