A history of viral infections of the central nervous system

For millennia, infectious diseases were viewed as the result of malignant supernatural forces or punishments by angry gods for human transgressions. In the 19th century several advances occurred. Medicine became based on clinical observations; Rudolph Virchow laid the foundation of cellular pathology; Louis Pasteur dismantled the notion of spontaneous generation, and Robert Koch established the fundamental techniques of bacteriology, together creating the revolutionary paradigm shift of germ theory. Virology was born in the last decade of the 19th century in the study of tobacco mosaic virus; the crucial characteristics were the capacity to pass through a bacteria-retaining filter and the need for living cells in which to replicate. In 1901 yellow fever was shown to be the first human disease to be caused by a “filterable virus.” In 1903 rabies would be the first disease of the nervous system to be determined to be viral in nature, and polio followed soon thereafter. Paradoxically, because no agent has yet been shown to be the cause, the modern study of epidemic encephalitis began with encephalitis lethargica in 1917. However, the flood gates of viral isolations opened in the 1930s for the arboviral encephalitides, using experimental primates and mice, starting with St. Louis encephalitis and Japanese encephalitis. Within a decade, the viral nature of aseptic meningitis and herpes simplex sporadic encephalitis was demonstrated. From the 1950s through the 1970s great interest in “slow viral diseases” arose as potential models for chronic diseases of the nervous system. The era of modern neurovirology has been characterized by two principal features. The first is the remarkable advances in technology – witness the use of polymerase chain reaction (PCR) for identifying infectious agents, magnetic resonance imaging (MRI) to image the nervous system, and the advance in therapeutics based on molecular medicine. The second has been the impact of emerging and re-emerging diseases – witness the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic, Nipah encephalitis, and the appearance of West Nile encephalitis in the western hemisphere.