Taxonomy and virion structure
The rabies virus belongs to the family Rhabdoviridae, genus Lyssavirus. This same genus includes related bat viruses (e.g., Lagos bat, Mokola, and Duvenhage viruses), which share a similar morphology with the classical pathogen and are mainly isolated in Africa.
The virion has a characteristic bullet-like shape, ranging from 75 to 180 nm in size. Its internal structure includes:
- Core — a helical ribonucleocapsid.
- Envelope — a lipoprotein supercapsid with glycoprotein spikes on the surface.
Genome and proteins: The genetic material is represented by a single-stranded linear negative-sense RNA. Associated with it is the nucleoprotein (protein N), which forms the capsid. Beneath the lipoprotein envelope lies the matrix protein M. Spikes composed of glycoprotein G are located on the virion surface. Additionally, the virus contains a polymerase complex including a large protein L and a phosphoprotein P (or NS), which are responsible for viral RNA synthesis.
Antigenic properties and immune response
The main antigen of the rabies virus is glycoprotein G. It forms the surface spikes of the virion and performs critical functions:
- ensures adsorption (attachment) to target cell receptors;
- facilitates the entry of the virus into the cell;
- possesses high antigenic and immunogenic properties.
In response to viral invasion, the body produces specific virus-neutralizing antibodies directed precisely against glycoprotein G. These antibodies can be detected using the neutralization test (NT).
Internal proteins (ribonucleocapsid) act as a group-specific antigen. To detect viral antigens, the immunofluorescence assay (IFA), complement fixation test (CFT), and precipitation test (PT) are used.
Life cycle (reproduction)
The reproduction process of the rabies virus takes place in the cell cytoplasm and includes several stages:
- Adsorption and penetration: the virus binds via glycoproteins to cellular receptors and enters the cell through clathrin-mediated endocytosis.
- Deproteinization: uncoating of the virus occurs within endosomes, after which the ribonucleocapsid is released into the cytoplasm.
- Biosynthesis (transcription and replication): viral RNA-dependent RNA polymerase synthesizes short positive-sense strands (mRNA) for protein translation and full-length positive-sense strands, which serve as a template to create new genomic negative-sense RNAs.
- Translation and processing: viral proteins are synthesized on cellular ribosomes. Glycoprotein G undergoes complex modification in the endoplasmic reticulum and Golgi apparatus, after which it is embedded in the cell membrane.
- Assembly and release: new copies of negative-sense RNA bind to proteins, forming the ribonucleocapsid. Mature virions exit the cell by budding through areas of the membrane containing viral glycoproteins.
Variants and diagnostics
Two variants of the rabies virus are distinguished; they are identical in antigenic structure but differ in biological properties:
- Wild (street) virus — circulates in nature, highly pathogenic for humans and animals.
- Fixed virus (virus fixe) — a strain artificially obtained by Louis Pasteur (via passages in rabbits). It has lost pathogenicity for humans, is not excreted in saliva, does not form specific intracellular inclusions, and is used to produce vaccines.
For virus cultivation, intracerebral inoculation of laboratory animals or cell cultures is used. An important diagnostic sign of the wild virus is the formation of specific eosinophilic inclusions in brain neurons — Babes–Negri bodies (1–15 µm in size), which consist of viral ribonucleoprotein.
The virus is rapidly inactivated by UV rays, heating (above 60 °C), alkalis, fat solvents, and proteolytic enzymes, but it withstands low temperatures well (from –20 to –70 °C).
Briefly: answers to topical questions
Along which neural pathways does the rabies virus spread from the bite site to the CNS?
The rabies virus spreads from the bite site to the central nervous system via the axons of peripheral nerves. Following initial replication at the portal of entry, the pathogen invades motor or sensory neurons. Further centripetal movement into the brain and spinal cord occurs via retrograde axonal transport along neural pathways. Upon reaching the CNS, the virus actively replicates in the neurons of the medulla oblongata, hippocampus, and other structures, after which its centrifugal spread to the periphery begins.
Which animals are the main reservoirs of the wild rabies virus in nature?
The main reservoirs of the wild rabies virus in natural foci are wild carnivorous animals, rodents, and bats.
- Predators — red fox (the main natural reservoir in Russia), wolves, raccoon dogs, arctic foxes, jackals, corsac foxes, badgers, skunks, and mongooses. They act as the primary vectors of infection.
- Small mammals — rodents (mice, rats), hedgehogs. They form the prey base for predators and participate in maintaining foci.
- Chiroptera — bats (including vampire bats), which are also the primary reservoir for other species of the genus Lyssavirus.
Through what pathways can the rabies virus be transmitted to humans?
The rabies virus is transmitted to humans predominantly through contact, but other routes of infection are also possible.
- Contact route (primary) — occurs via virus-contaminated saliva of infected animals through bites, as well as through contamination of broken skin (microtraumas), conjunctiva, and intact mucous membranes.
- Aerosol route — possible under specific conditions, such as visiting caves inhabited by infected bat colonies, or in laboratory settings.
- Alimentary route — a rare variant occurring when consuming meat from infected animals.
- Transplant route — transmission via transplantation of infected tissues (e.g., cornea).
Transplacental transmission of the pathogen is also not excluded.
What is specific post-exposure prophylaxis of rabies?
Specific post-exposure prophylaxis of rabies is carried out for the emergency induction of immunity before the virus penetrates the CNS and includes local wound care, vaccination, and, in severe injuries, passive immunization. Rabies vaccine, such as COCAV, is administered intramuscularly according to a schedule on days 0, 3, 7, 14, 30, and 90 after a bite. In case of multiple or deep wounds, as well as bites in dangerous locations (face, neck, hands), rabies immunoglobulin (RIG) is additionally administered on day 0 at a dose of 20 IU/kg. A combined course is also indicated for injuries inflicted by wild or agricultural animals.
Class and exam questions
What shape does the rabies virion have?
The rhabdovirus virion has a characteristic bullet-like shape measuring 75–180 nm.
Which antigen is responsible for the production of virus-neutralizing antibodies?
The surface glycoprotein G (supercapsid spikes) is responsible for the induction of virus-neutralizing antibodies.
What are Babes–Negri bodies?
These are specific eosinophilic cytoplasmic inclusions in neurons consisting of viral ribonucleoprotein. They are a key marker in the diagnosis of street rabies.
What is the difference between street virus and fixed virus?
Street virus circulates in nature and is highly pathogenic. Fixed virus was obtained artificially (by L. Pasteur), is safe for humans, does not form Babes-Negri bodies, and is used for vaccine production.
What else to study on this topic
- Pathogenesis of central nervous system involvement
- Principles of laboratory diagnostics of rabies (IFA, CFT)
- Specific prophylaxis: types of antirabic vaccines
- Mechanism of clathrin-mediated endocytosis of rhabdoviruses
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