The first clear-cut description of a virus-nerve cell interaction was made by Adelchi Negri in 1903 with the detection of cytoplasmic bodies (Negri bodies) in subsets of neurons in the brain from rabies-infected animals. A biographical sketch of Negri is given here; he was born in Perugia, Italy, in 1875 and died in Pavia in 1912. In 1900 Negri became assistant to Camillo Golgi, who encouraged him to study rabies-infected brains with histological techniques. The report of intraneuronal bodies described by Negri as specific for rabies stimulated an intense debate both concerning their diagnostic value and their nature. The diagnostic value was finally determined in a study by Negri's wife, Lina Negri-Luzzani, in 1913, while the viral nature of the bodies had to await the introduction of electron microscopy and immunohistochemistry. However, the true significance of the Negri bodies is still mysterious, since they only develop in subsets of infected neurons and occur mainly after infection with wild, so-called 'street', virus strains and not after infection with strains passaged in the laboratory, so-called 'fixed' strains.
Newborn hamsters were inoculated intracerebrally with measles virus materials from Lu 106 and Vero carrier cell lines. Extracellular and cell-associated materials from cultures incubated at 37 degrees C and at 33 degrees C were used. The lower temperature allows accentuated virus replication. No animals contracted acute encephalitis, but 8 animals developed advanced neurological disease (unsteady gait, serial myoclonic jerks, hypoactivity) 79 to 212 days after injection. Seven out of these 8 animals belonged to a group of 50 animals, which had been inoculated with cell-associated material from cultures incubated at 33 degrees C. Viral antigen and nucleocapsids were found in neurons and glial cells from diseased animals, which showed degenerative changes and inflammation, particularly in the mesencephalon. Some of these animals also had hydrocephalus, which, however, also occurred in many apparently healthy animals. Also this pathological alteration occurred most frequently (5 out of 11 animals examined 9--10 months after inoculation) in hamsters receiving cell-associated material from carrier cutlures incubated at 33 degrees C. Possible mechanisms for the appearance of hydrocephalus are discussed.
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