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A number of viruses share the unique tendency to primarily affect the human nervous system. Included in this group are the human immunodeficiency viruses (HIV-1 and HIV-2), herpes simplex viruses (HSV-1 and HSV-2), herpes zoster or varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), poliovirus, rabies, and several seasonal arthropod-borne viruses (Flaviviruses). Some of these are neurotropic, exhibiting an affinity for certain types of neurons: for example, poliomyelitis viruses and motor neurons, VZV and peripheral sensory neurons, and rabies virus and brainstem neurons. Yet others attack nonneuronal supporting glial cells; JC virus causing progressive multifocal leukoencephalopathy is the prime example. For many of the rest, the affinity is less selective in that all elements of the nervous system are involved. Herpes simplex, for example, may devastate the medial parts of the temporal lobes, destroying neurons, glia cells, myelinated nerve fibers, and blood vessels; and HIV may induce multiple foci of tissue necrosis throughout the cerebrum. These relationships and many others, which are the subject of this chapter, are of wide interest in medicine. In some conditions, the systemic effects of the viral infection are negligible; it is the neurologic disorder that brings them to medical attention.

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Pathways of Infection

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Viruses gain entrance to the body by one of several ways. Mumps, measles, and VZV enter via the respiratory passages. Polioviruses and other enteroviruses enter by the oral–intestinal route, and HSV enters mainly via the oral or genital mucosal route. Other viruses are acquired by inoculation, as a result of the bites of animals (e.g., rabies), ticks, mites, or mosquitoes (arthropod-borne or arbovirus infections). The fetus may be infected transplacentally by rubella virus, CMV, and HIV. In all these cases, viremia is an intermediate step to seeding the brain or CSF.

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Another pathway of infection is along peripheral nerves; centripetal movement of virus is accomplished by the retrograde axoplasmic transport system. HSV, VZV, and rabies virus utilize this peripheral nerve pathway, which explains why the initial symptoms of rabies occur locally, at a segmental level corresponding to the animal bite. It has been shown experimentally that HSV may spread to the CNS by involving olfactory neurons in the nasal mucosa; the central processes of these cells pass through openings in the cribriform plate and synapse with cells in the olfactory bulb (CNS). Another potential pathway is the trigeminal nerve and gasserian ganglion, however, the role of these pathways in human infection is not certain. Of the different routes of infection, the hematogenous one is by far the most important for the majority of viruses.

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Additionally, VZV resides in the sensory ganglia and becomes reactivated later in life, causing shingles decades after the primary infection that produces chicken pox. The JC virus also is latent in tissues, possibly the kidney and bone marrow, only to reemerge under conditions of immunosuppression, to infect the brain.

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Mechanisms of Viral Infections

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