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INTRODUCTION

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Many different viruses can invade the central nervous system and cause disease. This chapter discusses rabies, a viral encephalitis feared since antiquity that is still an incurable disease; slow virus infections; and transmissible spongiform encephalopathies—rare neurodegenerative disorders that are caused by unconventional agents called “prions.”

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RABIES

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Rabies is an acute infection of the central nervous system that is almost always fatal. The virus is usually transmitted to humans from the bite of a rabid animal. Although the number of human cases is small, rabies is a major public health problem because it is widespread among animal reservoirs.

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Properties of the Virus

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A. Structure
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Rabies virus is a rhabdovirus with morphologic and biochemical properties in common with vesicular stomatitis virus of cattle and several animal, plant, and insect viruses (Table 42-1). The rhabdoviruses are rod- or bullet-shaped particles measuring 75 × 180 nm (Figure 42-1). The particles are surrounded by a membranous envelope with protruding spikes, 10 nm long. The peplomers (spikes) are composed of trimers of the viral glycoprotein. Inside the envelope is a ribonucleocapsid. The genome is single-stranded, negative-sense RNA (12 kb; molecular weight 4.6 × 106). Virions contain an RNA-dependent RNA polymerase. The particles have a buoyant density in CsCl of about 1.19 g/cm3 and a molecular weight of 300–1000 × 106.

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Table Graphic Jump Location
TABLE 42-1Important Properties of Rhabdoviruses
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FIGURE 42-1

Structure of rhabdoviruses. A: Electron micrograph of bullet-shaped particle typical of the rhabdovirus family (100,000×). Shown here is vesicular stomatitis virus negatively stained with potassium phosphotungstate. (Courtesy of RM McCombs, M Benyesh-Melnick, and JP Brunschwig.) B: Schematic model of rabies virus showing the surface glycoprotein spikes extending from the lipid envelope that surrounds the internal nucleocapsid and the matrix protein lining the envelope. The nucleocapsid comprises the single RNA genome plus nucleoprotein and the polymerase proteins. (Reproduced with permission from Cowan MK, Talaro KP: Microbiology. A Systems Approach, 2nd ed. McGraw-Hill, 2009. © The McGraw-Hill Companies, Inc.)

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B. Classification
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The viruses are classified in the family Rhabdoviridae. Rabies viruses belong to the genus Lyssavirus, whereas the vesicular stomatitis-like viruses ...

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