Rhabdoviridae

Rabies Virus

Legend: Electron micrograph of rabies virus in brain cells at 64,000x magnification. The bullets surrounding the smoothe gray circle are rabies. The circle itself is the negri body, which can be seen with a light microscope. Courtesy of Dr. F.A. Murphy, UC Davis.

Historical notes

Rabies virus was recognized in Egypt before 2300 B.C. and was described by Aristotle in ancient Greece. It has been characterized by many as one of the oldest and most feared diseases of both animals and man. It is the most lethal of all infectious diseases and has the widest host range of any virus. It was also responsible for inspiring one of the most significant biomedical discoveries in history. In 1885 Louis Pasteur developed the rabies vaccine during a time when the nature of viruses was still a mystery. It was the success of this vaccine that inspired scientists to prevent infectious diseases by vaccination.

Introduction

The Rhabdoviridae family is comprised of over 150 viruses of vertebrates, invertebrates and plants. The Rhabdoviruses are approximately 70 nm wide and 170 nm long. They consist of a lipid envelope with glycoprotein peplomers surrounding a helically wound nucleocapsid. It is the arrangement of the peplomers and the nucleocapsid that give the virus its distinct bullet- shaped morphology. The viruses contain a single linear molecule of minus sense ssRNA, 11-12 kb in size. The pathogen that humans should be most concerned with is the rabies virus which is capable of infecting all warm blooded animals. Rabies occurs in most geographic regions but has been successfully eradicated in Australia, Japan, Great Britian, Hawaii, and the islands of the Carribean basin. Dog rabies is an important human concern as the virus in the saliva of infected dogs is responsible for majority of the 75,000 cases of human rabies that occur each year worldwide. The prevalence of wildlife rabies in the United States, Europe and Canada has become an increasing concern for humans in these geographic regions.

Transmission

The most common transmission of rabies is via the bite of a rabid animal which usually results in the deposition of rabies infected saliva into the striated muscle. Transmission of the virus can also occur after a superficial abrasion of the skin and in some environments, such as bat caves, where the amount of virus may be high, it can be transmitted via aerosol. Human to human transmission via saliva has been reported but has not been substantiated. The only form of human to human transmission has been iatrogenically via corneal transplantation from donors of undiagnosed rabies.

The virus initially replicates in the muscle cells or cells of the subepithelial tissue. Then when its concentration is sufficient to infect the motor and sensory nerves in the muscle or skin it binds the the acetylcholine receptors or other receptors entering the nerve endings. The virus is then delivered to the central nervous system via axons in the spinal cord.

The infected individual may experience two forms of the virus depending on the location of neuronal infection. Furious Rabies is exhibited when the virus replicates in the limbic system while Dumb Rabies is experienced when the virus replicates in the neocortex.

Clinical Features

Furious Rabies generally manifests as headache, fever, irritability,restlessness and anxiety. Muscle pains, salivation and vomitting may follow. A few days following exposure the patient may experience a stage of excitement or muscle spasms initiated from the ingestion of of saliva or water. As a result these individuals have a tendency to drool and begin to fear water-hydrophobia. This excited phase continues for a few days until the patient lapses into a coma and dies.

Dumb Rabies manifests itself in the opposite manner as Furious Rabies . Instead of demonstrating excitement the patient experiences depression and paralysis followed by a coma. Death eventually results from respiratory arrest. This form of the virus is often difficult to diagnose from a clinical perspective.

Prevention

The measures used by different geographic regions varies and is determined by whether the area is free of the disease, if the country is industrialized or developing and the incidence of bat rabies in the area.

Rabies free countries are maintained by enforcing strict quarantine regulations of dogs and cats for 6 months. In developing countries, where rabies is a serious problem, large doses of human vaccines are administered. In addition, stray domestic animals are strictly monitored, dogs and cats are immunized to break the chain of viral transmission and public education programs are promoted.

In industrialized countries the control of rabies in wildlife is generally based on the animal population. The immunization of wildlife species has shown to decrease the prevalence of rabies in Switzerland and Germany. The administration of more wildlife vaccinations will be determined by the population density of the target species, research analyzing the efficacy of orally ingested wildlife vaccines as well as the appropriate delivery system for each reservoir.

Bat rabies has been a problem in humans and livestock in several countries of Latin America. Bovine vaccines and anticoagulants have been administered to solve the problem. These drugs cause the rabid bats to suffer fatal hemorrhages in their wing capillaries when they feed off the blood of the treated cattle.

Vaccination

Rabies is the only human disease that can be treated by a postexposure vaccination. This form of treatment is can be utilized because the time of infection is generally known by the victim and the incubation period for the disease is long. The vaccines utilized are live attenuated vaccines. People at risk for acquiring rabies should be immunized with a vaccination and also be administered rabies immune globulin intramuscularly and around the bite. If the vaccine and the immune globulin is administered promptly after infection the mortality of the disease will be decreased from 100% to zero. Individuals catagorized as "high risk" for rabies include laboratory personnel working with the rabies virus, veterinarians, animal control and wildlife workers and travelers visiting areas where rabies is known to exist.

Vesicular Stomatitis

The vesicular stomatitis virus is a member of the rhabdovirus family. It is a zoonotic virus and is transmissible to humans from the vesicular fluids and tissues of infected animals. Veternarians and farmers are at the greatest risk. There is no practical way to prevent occupational exposure. The disease resembles influenza and resolves without complications within 7-10 days. VSV has been used to elucidate the process of protein targeting.

Useful web links

References

Medical Virology
David White and Frank Fenner
Fourth Edition
Academic Press
New York 1994

The Humans and Viruses Course Reader
Human Biology 115A
Robert Siegel M.D. PhD.

Stephanie Dollens

Created: February 1, 1998
Last modified: March 3,1998