Last updated on June 6th, 2021
Rabies is an infectious viral disease caused by Rabies virus. It affects humans as well as domestic and wild animals.
Rabies virus is an enveloped, single-stranded RNA virus with bullet- shaped or rod-shaped morphology. It is the member of the family Rhabdoviridae and the genus Lyssavirus.
Structure of Rabies virus
Shape: Rabies virus is rod or bullet- shaped (75 x 180 nm); one end conical, other planar ( concave).
Envelope: Present. Virus envelope contains glycosylated G-protein spikes embedded in lipid membrane derived from the host cell. This envelope doesn’t cover the planar end.
Matrix (M) protein: Membrane or matrix (M) protein layer lies beneath the envelope. Virus nucleoprotein (N) which tightly binds the viral RNA to form the nucleocapsid core lies inside to matrix protein.
Viral genome: The core of the virion consists of helical RNP (group-specific antigen). Genome is unsegmented, linear, ss (-) sense RNA ( 12kb, MW 4.6 X 106) and the virion contains an RNA-dependent RNA polymerase.
- survives at 4°C for weeks and at -70°C for years.
- Sensitive to ethanol, iodine- preparations, 40– NH4+ compounds, soap, detergents, and lipid solvents (ether, chloroform, acetone).
- Inactivated by phenol, formalin, ß- propiolactone( BPL), UV or sunlight; thermal inactivation at 50°C in 1 hr, and at 60°C in 5 minutes.
- Inactivated by CO2, so, for storage in dry ice, it should be sealed in glass vials.
- Attachment: Rabies virus attaches to host cells via its glycoprotein spikes; nicotinic acetylcholine receptor may serve as a cellular receptor (in neurons).
- Entry: Entry is by endocytosis.
- Replication and Assembly:
- Viral RNA polymerase transcribes viral genome into 5 mRNA species; the monocistronic mRNA species code for 5 virion proteins: nucleocapsid (N), polymerase proteins (L,P), matrix (M), and glycoprotein (G).
- Genome RNP is a template for complementary (+) sense RNA, which is responsible for a generation of (-) sense progeny RNA. Same viral protein serves at polymerase for viral RNA replication as well as transcription.
- newly replicated genomic RNA associates with viral transcriptase and nucleoprotein to form RNP cores in the cytoplasm; M- protein is important in packaging the RNA.
- Release: The newly formed virus particles acquire an envelope by budding through the plasma membrane.
Animal Susceptibility and Growth of Virus
- Rabies virus has a wide host range; all warm-blooded animals including human can be infected. Susceptibility varies; high (fox, wolves, bats, cats), to moderate ( dogs, sheep) to low ( opossums).
- Virus is widely distributed in the nervous system, saliva, urine, lymph, milk and blood of infected animals.
- When freshly isolated in lab, strains are referred to as “ street virus”; these cause fatal encephalitis in lab animals following inoculation by any route, after a long and variable incubation period ( 1-12 weeks) and regularly produce intracytoplasmic inclusion bodies (Negri bodies).
- Serial brain to brain passage in rabbits of the street virus yields a fixed virus that no longer multiplies in extraneural tissues; after intracerebral inoculation, it produce fatal encephalitis after a short and fixed incubation period of 6.7 days; negri bodies usually not demonstrable.
There is a single serotype of rabies virus; however there are strain differences among viruses isolated from different species.
- substitution at amino acid position 333 of gp results in loss of virulence, where Arg has replaced Gln or Ile in the more pathogenic variant.
- purified spikes containing viral gp elicit neutralizing( protective) antibody; thus provide a safe and effective subunit vaccine.
- antiserum prepared against purified nucleocapsid Ag used in diagnostic IFT, the antibody is not protective and is group-specific.
- virus possesses haemagglutinating activity (property of gp spike), optimally seen with goose erythrocytes at 0-4°C and PH 6.2.
- GP spikes are inactivated by heat ( 56°C for 30-60 min), ether, trypsin, deoxycholate or tween 80, but not by BPL.
Human to human transmission is very rare, only documented cases involve transmission by corneal transplants. The virus does not penetrate intact skin, and if deposited it is inactivated due to time and drying. Uncommon routes for transmission are:
- Inhalation while in bat- infested cave
- aerosols released during centrifugation of infected materials in the lab
- Ingestion of flesh of rabid animals (high dose would be necessary)
Rabies virus multiplies in muscle or connective tissues at the site of inoculation for 48- 72 hrs → enters peripheral nerves at neuromuscular junction → spreads up the nerves to CNS → multiplies in the CNS and progressive encephalitis develops → spreads centrifugally along the peripheral nerve trunk to various body parts including the salivary glands where it multiplies and is shed in saliva; organ with the highest titer of virus is submaxillary gland. Other organs where virus has been found include pancreas, kidney, heart, retina, and cornea; Rabies virus has not been isolated from blood. Susceptibility to infection and incubation period depends on
- hosts age, genetic background and immune status;
- viral strain involved,
- amount of inoculum,
- the severity of laceration, and
- the distance between point of entry and CNS
Virus produces a specific eosinophilic cytoplasmic inclusion, the Negri body in infected nerve cells, which are round or oval, purplish pink structure and vary in size from 3-27 µm; the Negri bodies are filled with viral nucleocapsids. Presence of such inclusions is pathognomonic of rabies, but it is not observed in at least 20% of cases; therefore the absence of Negri bodies does not rule out rabies as a diagnosis.
Rabies viral disease is acute, fulminant, fatal encephalitis, primarily a disease of lower animals; spread to humans by bites of rabid animals or by contact with saliva. Incubation period is typically 1-2 month; may be as short as 1 week or as long as yrs Clinical spectrum can be divided into 3 phases
- short prodrome.
- acute neurologic (encephalitic) phase
- coma / deathprodrome lasting 2-10 days may show malaise, anorexia, headache, photophobia, nausea and vomiting, sore throat, fever; there is profound sense of apprehension, anxiety, agitation, irritability, insomnia or depression.
During the acute neurologic phase( 2-7 days), there are signs of nervous system dysfunction which begins with hyperactivity → bouts of bizarre behaviour, agitation or seizures.
• pathognomic feature is difficulty in drinking, together with intense thirst; attempts to drinking may bring painful spasms of pharynx / larynx producing choking and gagging, patients develop a dread of even the sight or sound of water ( hydrophobia).
• generalized convulsions follow death occurs with in 1-6 days due to respiratory arrest during convulsion.
- Rabies may present as:
- furious rabies: predominantly encephalitic disease with neurologic dysfunction.
- dumb rabies: paralytic illness; with symmetrical ascending paralysis followed by coma and death, occurs in about 20% patients.
Pathogenicity of a strain related to its capacity to induce cell fusion in neuroblastoma cells. Observable damage to nerve cells in the brain appears minimal; non-specific changes include parenchymal microglial response and perivascular cuffing, with lymphocyte and plasma cell infiltration in the grey matter of brain stem and spinal cord.