Rabies Virus

Enveloped, single-stranded negative-sense RNA viruses that form helical nucleocapsids. The pathogenic viruses that we'll learn about in this tutorial are zoonotic. Rhabdoviruses: Rabies Rod-shaped; "rhabdo" means "rod." Genome encodes only 5 genes. Helical nucleocapsid gives the virion a striated appearance under electron microscope. Lyssavirus genus includes Rabies and Rabies-like viruses** Filoviruses: Hemorrhagic fever Formerly included in the Rhabdoviridae. Pleomorphic; appear as long, short, or branched filaments. Marburg virus and Ebola virus are key pathogenic viruses that cause hemorrhagic fever. Causes an acute, fatal nervous system infection. 1. Viral inoculation: The virus is most often transmitted via a bite or scratch from an infected animal Infection in animals produces aggressive behavior that promotes transmission via bites or scratches. More rarely, aerosolized virions are inhaled or the virus is obtained from infected tissue transplants. Worldwide, unvaccinated dogs are the major sources of human rabies infections. Because of widespread canine vaccination programs in the United States, cats and undomesticated carnivores (raccoons, bats, etc.) are the primary reservoirs. 2. Replication in local muscle tissue; or, the virus can enter the peripheral nervous system, directly. 3. Retrograde axonal transport. Upon entering peripheral nerves, the virus uses retrograde axonal transport to reach the central nervous system. Current research suggests that rabies virions bind with acetylcholine receptors, neural cell adhesion molecules (NCAM), and other neural receptors. 4. Replication in dorsal ganglions. 5. Ascension to structures in the brain and brainstem. 6. CNS infection & replication. Rabies virus infects and replicates within central nervous structures, which can produce encephalitis. Negri bodies are cytoplasmic inclusion bodies that contain viral proteins and RNA. Be aware that the presence of Negri bodies is variable, and, that they are especially found in the pyramidal cells of the hippocampus (specifically, in Ammon's horn) and in Purkinje cells of the cerebellum. Perivascular cuffing occurs when the virus triggers inflammatory cell accumulation around blood vessels. 7. Virus descends to infect the skin, glands, and other organs. The virus specifically travels to and infects the salivary glands. In non-human animals, migration to the salivary glands is key for transmission via saliva. 5 stages of rabies virus infection in humans 1. Incubation stage. Typically lasts 1-3 months, but is highly variable, and can last much longer. – Duration of the incubation period is related to the distance between the inoculation site and the CNS, as well as host and viral factors. 2. Prodrome stage lasts for 2-10 days, and is marked by the appearance of nonspecific symptoms and tingling or pain at the wound site. Some patients experience respiratory, gastrointestinal, or central nervous symptoms. 3. Neurologic stage is characterized by symptoms of "furious" and/or "paralytic" rabies: Furious, aka, encephalitic rabies = Hyperactivity (agitation, mania) and hydrophobia. Hydrophobia, which is fear or avoidance of water, is attributed to painful spasms of the pharyngeal muscles used for swallowing. Paralytic, aka, "dumb" rabies = Flaccid paralysis. Patients with these symptoms are often misdiagnosed. The end of this phase is marked by irregular, rapid breathing. 4. Coma. 5. Death due to cardio-respiratory arrest. Very few survive rabies infection without prompt immunization. Best prevented via widespread canine and other animal vaccination programs. At-risk humans, such as veterinary or lab workers, can receive pre-exposure immunization. Fatal without vaccination prior to the appearance of neurologic symptoms.