Rabies virus

Definitions & Key takeaways

The rabies virus is a single-strand RNA virus from the rhabdovirus family, known to affect the nervous system of mammals, including humans. The rabies virus is transmitted by animal saliva, particularly from wildlife in developed countries and dogs in developing countries. After a bite from an infected animal, the virus travels in neurons in a retrograde fashion from the peripheral nervous system to the brain. After a long incubation period, the virus causes symptoms like fever and paresthesia, followed by encephalitic rabies, which causes hydrophobia, overactivation of the autonomic nervous system, aggressive behavior, and ascending paralysis. Post-exposure treatment involves wound cleaning, passive immunization, and a vaccine. When the symptoms appear before treatment is given, the virus becomes fatal.

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Rabies virus, formally called Rabies lyssavirus, affects the central nervous system and causes encephalitis, or acute inflammation of the brain.
It’s a viral infection transmitted by infected animals, like dogs and bats, and once symptoms develop, it’s usually fatal.The rabies virus is part of the rhabdoviridae family of viruses.
All rhabdoviruses are single-strand RNA viruses surrounded by a helical capsid, or a helix-shaped protein layer, all within a distinct bullet-shaped outer envelope, which is covered in glycoprotein spikes.
They’re also negative sense RNA viruses, which means that before it can be used to make proteins their genetic material has to be transcribed into mRNA.
And these viruses carry their own RNA polymerase to do just that. To understand how rabies works, first let’s look at the human nervous system.
The nervous system is divided into the central nervous system, so the brain and spinal cord, and the peripheral nervous system, which includes all the nerves that connect the central nervous system to the muscles and organs.Neurons, the main cells of the nervous system, have nerve fibers that extend out from the neuron cell body- these are either dendrites that receive signals from other neurons, or axons that send signals along to other neurons.
Where two neurons come together is called a synapse, and that’s where one end of an axon releases neurotransmitters, further relaying the signal to the dendrites or directly to the cell body of the next neuron in the series.
Some synapses allow neurons to relay signals to other types of cells, like the neuromuscular junction where motor neurons innervate muscle cells by releasing the neurotransmitter acetylcholine.
Acetylcholine binds to nicotinic receptors on the muscle cell membrane, which are ion channels that open when acetylcholine binds to them; and they allow positive ions like sodium and calcium to cross the cell membrane, triggering a muscle contraction.Rabies most frequently enters the body via animal saliva from a bite, but sometimes it can be caught from air droplets, like in a bat cave.
Then, the glycoprotein spikes on its envelope bind to the nicotinic acetylcholine receptors on the plasma membrane of muscle cells, allowing the virus to enter the muscle cells.
But rabies really prefers neurons to muscle cells, so it crosses the neuromuscular junction and enters motor neurons, where it replicates.
Then, it uses dynein, a motor protein found in the neuron’s cytoplasm, to slowly move a few millimeters each day in a retrograde direction up peripheral nerves - meaning towards the central nervous system.
When it reaches the CNS, it invades the brain and spreads to other structures, like the salivary glands. On microscopy, CNS cells infected with rabies have inclusion bodies, which are basically little intracellular sacs full of viral proteins.
With rabies, they’re called Negri bodies, after the pathologist who discovered them, and they’re usually found in the cell body of Purkinje cells of the cerebellum and the pyramidal cells of the hippocampus.
They are eosinophilic, meaning they can be stained with an eosin dye, making them dark pink. Now the stereotype of rabies transmission is catching it from a dog bite, which is still the norm in developing countries, but in developed regions it’s usually transmitted by wildlife, particularly bats, raccoons, skunks, and foxes.
The rabies virus has an incubation period that lasts an average of 1 to 3 months, and this depends largely on where it enters the body - the farther from the CNS, the longer before symptoms appear.
In the early phase, symptoms are usually malaise, headache, fever, and paresthesia, or a sensation of tingling, itching, or burning that radiates from the original site of infection.
In the clinical phase, there are two typical types of symptoms. Encephalitic, or furious, rabies, the most common type, involves fever, hydrophobia, or fear of water, and foaming at the mouth from uncontrollable spasms of the pharynx whenever the person tries to drink.
Other symptoms include excessive saliva production, sweating, and dilated pupils from an overactive autonomic nervous system.
The person can become agitated and aggressive, and eventually goes into a coma. Paralytic rabies, which is far less common, involves paralysis that moves up the body.
In both types, the virus is usually fatal, and death is caused by respiratory failure from either spasms or paralysisDiagnosis of rabies antemortem, or before the person dies, requires multiple laboratory tests because no one test is sensitive enough.
Reverse transcriptase polymerase chain reaction, or RT-PCR, is used to look for viral RNA in saliva. Immunofluorescence staining can be done on a skin biopsy from the back of the neck to look for viral antigen - which is typically found in cutaneous nerves in hair follicles.
We can also look for antibodies to the rabies virus in blood and cerebrospinal fluid samples. After death, rabies is diagnosed by looking for Negri bodies and viral antigens in brain cells.Post-exposure treatment for rabies includes wound cleaning, passive immunization by giving human rabies immunoglobulin, and a killed vaccine for the development of active immunization.
This post-exposure prophylaxis can be given up to the time that the first symptoms appear. After symptoms develop, it’s no longer effective and usually only palliative treatment is given.
In terms of prevention, the rabies vaccine is only given preemptively to groups that are at risk of exposure like veterinarians and lab workers who work with the rabies virus.
##SummaryAll right, as a quick recap… The rabies virus is a single-strand RNA virus from the rhabdovirus family. It infects neurons, moving in a retrograde fashion from the peripheral nervous system to the brain.It’s transmitted by animal saliva, particularly from wildlife in developed countries and dogs in developing countries.After a long incubation period, it will cause symptoms like fever and paresthesia, followed by either encephalitic rabies, which causes hydrophobia, overactivation of the autonomic nervous system, and aggressive behaviour, or paralytic rabies, which causes ascending paralysis.Post-exposure treatment involves wound cleaning, passive immunization, and a killed vaccine.If symptoms appear before treatment is given, the virus is fatal.