Abstract
The central nervous system (CNS) is a highly complex network comprising long-lived neurons and glial cells. Accordingly, numerous mechanisms have evolved to tightly regulate the initiation of inflammatory responses within the brain. Under neuroinflammatory conditions, as in the case of viral encephalitides, the infiltration of leukocytes is often required for efficient viral clearance and recovery. The orchestration of leukocyte migration into the inflamed CNS is largely coordinated by a large family of chemotactic cytokines and their receptors. In this review, we will summarize our current understanding of how chemokines promote protection or pathogenesis during arbovirus induced encephalitis, focusing on neurotropic flaviviruses and alphaviruses. Furthermore, we will highlight the latest developments in chemokine and chemokine receptor based drugs that could have potential as therapeutics and have been shown to play a pivotal role in shaping the outcome of disease.
Highlights
Arboviruses are a significant cause of human morbidity and mortality and have worldwide distribution
There are vaccines available for the prevention of Japanese encephalitis virus (JEV) and tick borne encephalitis virus (TBEV) infection, no vaccines exist for human West Nile virus (WNV) infection, and no specific therapeutics are currently available for the treatment of neuroinvasive diseases caused by any arbovirus
There is an urgent need for novel intervention strategies, either in the form of antivirals or immunomodulators that can block viral replication, boost protective immune responses, and minimize central nervous system (CNS) injury
Summary
Arboviruses (arthropod-borne viruses) are a significant cause of human morbidity and mortality and have worldwide distribution. Chemokines play a pivotal role in the attraction of leukocytes into the CNS, and it is imperative to understand their cell-type specific role in pathogenesis in order to develop novel immunotherapeutics and predict the impact of chemokine receptor antagonism in humans. Chemokines and their receptors comprise a large superfamily of proteins that can be categorized into four subfamilies based on the position of the first two cysteines within the first amino terminal cysteine motif: CC, CXC, XC, and CX3C (Zlotnik and Yoshie, 2000). We will focus on WNV, JEV, TBEV, SFV, and SINV, as Frontiers in Cellular Neuroscience www.frontiersin.org
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