Neuronal CCL2 expression drives inflammatory monocyte infiltration into the brain during acute virus infection

Charles L Howe; Reghann G. LaFrance-Corey; Emma N Goddery; Kanish Mirchia

Neural injury associated with virus infection represents a multifaceted convergence of hostpathogen interactions that range from direct lytic killing of infected neurons to bystander pathology mediated by brain-infiltrating immune cells responding to chemotactic and inflammatory cues. Viral encephalitis is a trade-off between the need to clear pathogen from the brain and the need to preserve irreplaceable neurons and neural circuits: too little inflammation and the host dies of uncontrolled infection, too much inflammation and the host suffers permanent brain damage [1] . And while much attention is rightly given to viral encephalitides associated with human mortality, there is likely a significant component of neural injury associated with low-level, sub-clinical viral infections of the central nervous system that are ultimately cleared by the host. Theiler's murine encephalomyelitis virus (TMEV) is a model of such an infection [2] . When C57Bl/6 mice are inoculated via intracranial delivery of the Daniel's strain of TMEV there is an acute viral encephalitis that culminates in generation of an antiviral T cell-mediated response, development of virus neutralizing antibodies, clearance of the virus, and resolution of brain inflammation over the course of about 45 days [3] . However, despite essentially complete resolution of the infection, permanent neurological sequelae such as impaired spatial learning [2, 4] , anxiety [5] , and epilepsy [6] occur in most post-infectious animals. Uniquely, these neurologic problems largely stem from bystander loss of CA1 pyramidal neurons and subsequent disruption of hippocampal and hippocampal-cortical circuits [4, 7, 8] .