Viral diseases of the central nervous system

Abstract

Virus-induced diseases of the central nervous system (CNS) represent a significant burden to human health worldwide. The complexity of these diseases is influenced by the sheer number of different neurotropic viruses, the diverse routes of CNS entry, viral tropism, and the immune system. Using a combination of human pathological data and experimental animal models, we have begun to uncover many of the mechanisms that viruses use to enter the CNS and cause disease. This review highlights a selection of neurotropic viruses that infect the CNS and explores the means by which they induce neurological diseases such as meningitis, encephalitis, and myelitis.

Figure 1. Immunopathogenesis of fatal meningitis induced by LCMV

A) On day 5 post-infection, small numbers of antiviral CD8⁺ T cells begin to infiltrate the subarachnoid space and engage virus-infected targets such as meningeal stromal cells, leading to chemokine release. There is little pathology in the meninges and brain parenchyma at this time point, although reactive microglia can be observed. B) On day 6 post-infection, large numbers of CD8⁺ T cells migrate into the subarachnoid space, which amplifies chemokine release and gives rise to massive, synchronized extravasation by innate myelomonocytic cells. This results in disruption of vascular tight junctions, breakdown of the glial limitans, cellular pathology, edema, and ultimately death.

Figure 2. Brain regions affected by viruses that cause meningitis and encephalitis

Abbreviations: AV, alphaviruses, BV, bunyaviruses, CMV, cytomegalovirus, HEV, human enteroviruses, HIV, human immunodeficiency virus, HSV, herpes simplex virus, JCV, John Cunningham virus, JEV, Japanese encephalitis virus, LCMV, lymphocytic choriomeningitis virus, MeV, measles virus, Mumps, Mumps virus, Nipah, Nipah virus, PV, poliovirus, RV, rabies virus, SLEV, St. Louis encephalitis virus, TBEV, tick-borne encephalitis virus, WNV, west nile virus.

Figure 3. Spinal cord regions affected by viruses that cause myelitis

Abbreviations: HEV, human enteroviruses, JEV, Japanese encephalitis virus, PV, poliovirus, RV, rabies virus, TBEV, tick-borne encephalitis virus, WNV, West Nile virus.