Enterovirus and Encephalitis

Abstract

Enterovirus-induced infection of the central nervous system (CNS) results in acute inflammation of the brain (encephalitis) and constitutes a significant global burden to human health. These viruses are thought to be highly cytolytic, therefore normal brain function could be greatly compromised following enteroviral infection of the CNS. A further layer of complexity is added by evidence showing that some enteroviruses may establish a persistent infection within the CNS and eventually lead to pathogenesis of certain neurodegenerative disorders. Interestingly, enterovirus encephalitis is particularly common among young children, suggesting a potential causal link between the development of the neuroimmune system and enteroviral neuroinvasion. Although the CNS involvement in enterovirus infections is a relatively rare complication, it represents a serious underlying cause of mortality. Here we review a selection of enteroviruses that infect the CNS and discuss recent advances in the characterization of these enteroviruses with regard to their routes of CNS infection, tropism, virulence, and immune responses.

Keywords: CNS; Picornaviridae; RNA virus; encephalitis; enterovirus.

FIGURE 1

The pathways through which enteroviruses can gain access to the CNS. Enteroviruses can invade the CNS through three pathways. First, they infect BMECs, compromising and crossing the BBB to reach the CNS directly. The second pathway is known as Trojan horse route, in which enterovirus-infected leukocytes act as carriers and transverse the brain barriers bringing virus into the CNS. Thirdly, enteroviruses are able to hijack the retrograde axonal transport to enter the CNS from muscles into the motor neurons in the spinal cord.

FIGURE 2

The regions of the CNS affected by enteroviruses that cause encephalitis, meningitis and AFP. The CNS is composed of cerebrum, diencephalon, cerebellum, brainstem, and spinal cord. Following enteroviral infection of the CNS, inflammation can occur in different anatomical regions such as the brain (encephalitis), meninges (meningitis), and spinal cord (myelitis), or simultaneously in multiple regions (meningoencephalitis, encephalomyelitis).