Viral routes and host defenses

Many viruses once they reach the central nervous system (CNS) are capable of infecting cells and producing varying types of clinical syndromes. If the virus infects primarily meningeal cells lining the brain, meningitis develops. If the virus widely infects many types of brain cells, such as neurons and glia, encephalitis ensues. Some viruses infect only selective cell types producing specific clinical syndromes. For example, poliovirus infects only neurons of the motor pathway producing a paralytic disease called poliomyelitis. To date, viruses have not been implicated as a cause of brain abscesses or subdural empyemas.

Viral infections of the CNS usually begin with a primary focus of infection associated with their route of entry. Enteroviruses establish an initial infection in the gastrointestinal tract. Mumps virus establishes a primary infection in the respiratory tract. Rabies virus is directly inoculated through the skin via saliva during the bite from an infected animal and establishes a primary infection in the subcutaneous tissue and underlying muscle. Arboviruses are inoculated through the skin by a vector (infected mosquito or tick) and infect subcutaneous tissue and traversing blood vessels. The primary systemic infection usually is asymptomatic but prodromal syndromes can occur (gastroenteritis or upper respiratory infection). As viral replication continues at the primary site of infection, progeny virions spread into adjacent blood vessels or lymphatic channels. A viremia of varying duration then develops seldom causing a CNS infection. For example, less than 2% of susceptible individuals infected with poliovirus develop viral infection of the spinal cord and paralysis (Melnick, 1996).

For a viremia to cause a CNS infection, several important host barriers must be overcome. The reticuloendothelial system (RES) is an efficient filter of viruses circulating in blood. Clearance of small viruses, such as arboviruses, from blood is over 90% within 1 hour. However, some viruses overcome the RES by constantly releasing viral particles into the bloodstream following infection of vascular endothelial cells or lymph nodes (Johnson & Mims, 1968). Other viruses circumvent the RES by infecting circulating blood cells. Mumps virus can replicate within leukocytes and human immunodeficiency virus (HIV) can replicate in T-helper lymphocytes and monocytes/macrophages. In this manner, viruses are protected by RES phagocytosis or circulating neutralizing antibody.