4. Rabies

Causative agent of Rabies

is the rabies virus, a neurotropic virus belonging to the Lyssavirus genus, primarily transmitted through bites from infected animals.

Why do 80% of rbies deaths occur in poor regions

lack of vaccination in dogs and lack of post exposure treatment

Mortality rateonce symptoms appear

100%

What animal transmits 90% of rabies infections

dogs

Rabies carriers

MAMMALS: bats, dogs, cats, and foxes

Rabies transmission

infected saliva comes into contact with muscle cells through bite

Where does the lyssavirus genus get its name

Lyssa, the greek goddess of rage

What does it mean that rabies virus is neurotropic

It means that the rabies virus has a preference for infecting nerve cells, leading to neurological symptoms.

Rabies virus genome

-ss RNA

Rabies virus shape

bullet shaped

Nucleoprotein

encapsulates RNA genome

Nucleocapsid

RNA genome, polymerase, and phosphoprotein, surrounded by nuceloprotein

Phosphoprotein

cofactoer for polymerase and disrupts host antiviral defense

Matrix protein

bridge between nucleocapsid and viral envelope

Glycoprotein

Ligand for cellular reception

How does RABV get inside muscle cells

G-protein interats with nicotinic acetyl choline receptor to trigger phagocytosis and allow viral entry into muscle cells.

What is occuring during the prolonged incubation period

virus is replicating in muscle cells to build up genomic RNA and produce viral proteins.

Where does the virus go after it replicates in the nuscle cell

to the neuromuscular junction, enters motor neurons.

Retrograde axonal transport

is the process by which rabies virus travels along the axon of motor neurons towards the cell body after entering through the neuromuscular junction. Making its way from PNS to CNS

Once the bain is infected what happens

Virus spread to other organs and tissues including salivary gland and heart

RABV immune evasion

Type 1 IFN inhibits immune system (P protein)
Decreases PAMP recognition (N protein)
BBB restricts immune access

Prodromal phase of rabies

is the initial stage of rabies infection where symptoms such as fever, headache, and malaise appear, typically lasting for 2 to 10 days before more severe symptoms develop.

Acute neurological phase of infection

is characterized by severe neurological symptoms including confusion, agitation, hallucinations, and paralysis, which can progress rapidly and indicate severe brain involvement.

Acute neurological phase- furious (80%)

encephalitic rabies which presents with hyperactivity, agitation, and aggressive behavior. Symptoms may escalate quickly, leading to seizures and paralysis.

Acute neurological phase- paralytic (20%)

take longer to develop, but gradual paralysis occurs, then coma and death from cardirespiratory arrest

WHy does rabies travel to the heart after the brain

RABV enters cardiomyocytes to cause inflammation
Likely contributes to death

Rabies diagnosis- gold standard

fluorescent antibody test (FAT) to detect rabies virus in tissues.

Rabies treatment

No effective treatment once symptoms start
Only palliative care and symptom management

Pre-exposure prophylaxis (PrEP)

Inactivated viral vaccine for high risk groups
But very expensive and will only SLOW IT DOWN

Post-expsure prophylaxis (PEP)

Wound care, vaccine, and human rabies imune globulin to prevent rabies from jumping to brain
Nearly 100% success rate but very expensive

Vaccine limitations

hard to make long term vaccine due to glycoprotein which has so much variability