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INTRODUCTION

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The dog was certainly rabid. Joseph Meister had been pulled out from under him covered with foam and blood.

—Louis Pasteur, describing the 9-year-old boy he successfully immunized against rabies in July, 1885

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Rabies is an acute fatal viral illness of the central nervous system (CNS). The word rabies is derived from the Latin verb “to rage,” which suggests the appearance of the rabid patient. It can affect all mammals and is transmitted between them by infected secretions, most often by bite. It was first recognized more than 3000 years ago and has been the most feared of infectious diseases. It is said that Aristotle recognized that rabies could be spread by a rabid dog.

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VIROLOGY

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The rabies virus is a rhabdovirus, which is a bullet-shaped, enveloped, RNA virus, 70 nm in diameter × 180 nm in length, of the Lyssavirus genus and Rhabdoviridae family (Figure 17–1). The helical nucleocapsid (N) is composed of a single-stranded, negative-sense RNA genome and an RNA-dependent RNA polymerase enclosed in a matrix (M) protein covered by a lipid bilayer envelope containing knob-like glycoprotein (G). The knob-like glycoprotein excrescences, which elicit neutralizing and hemagglutination-inhibiting antibodies, cover the surface of the virion. In the past, a single antigenically homogeneous virus was believed to be responsible for all rabies; however, differences in cell culture growth characteristics of isolates from different animal sources (bats, cats, dogs, foxes, skunks), some differences in virulence for experimental animals, and antigenic differences in surface glycoproteins have indicated strain heterogeneity among rabies virus isolates. These studies may help to explain some of the biologic differences as well as the occasional case of “vaccine failure.” Other pathogens in the rhabdovirus group include vesicular stomatitis virus, which is an animal virus but may also occasionally infect humans (see Chapter 16).

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FIGURE 17–1.

Electron micrograph of the rabies virus (yellow) (×36,700). Note the bullet shape. The external surface of the virus contains spike-like glycoprotein projections that bind specifically to cellular receptors. (Reproduced with permission from Willey J, Sherwood L, Woolverton C (eds). Prescott's Principles of Microbiology. New York: McGraw-Hill; 2008.)

Graphic Jump Location
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Enveloped RNA virus is bullet shaped

Knob-like envelope glycoproteins elicit neutralizing and hemagglutination antibodies

Strains from different sources (animals) are antigenically heterogeneous

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Rabies virus is transmitted from the bite of an animal (usually a rabid dog or wild animal) and multiplies initially at the site of entry in muscle cells, and then the virus travels to the CNS to replicate in the brain cells. Rabies virus G protein binds to the acetylcholine or neural cell adhesion molecule (NCAM) receptor present on the cell surface. The virus is internalized followed by fusion of the viral envelope with the endosomal membrane and uncoating and release of the nucleocapsid in the cytoplasm. Because rabies virus is a negative-sense ...

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