Rabies ppt.ppt

Rabies virus, scientific name Rabies lyssavirus, is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. Rabies lyssavirus, like many rhabdoviruses, has an extremely wide host range.

1. Rabies, Slow Virus
Infections and Prions

2. Rhabdoviruses
•Features
•Bullet-shaped(75 x 180 nm)
•Enveloped
•Single stranded RNA genome, 12 kb
•Many viruses with broad host ranges
•Classification
•Family Rhabdoviridae
•Genus Lyssavirus(including
Rabies virus)
•Vertebrates
•Invertebrates
•Plants
•Genus Vesiculovirus(Vesicular
stomatitis-like viruses)

3. Rabies Virus
•Rabies virus replication
•Spike protein mediates
attachment (nicotinic
acetylcholine receptor)
•Viral RNA polymerase
transcribes a monocistronic
mRNA
•Five polypeptides are encoded by
the genome
•N
•L (polymerase)
•P (polymerase)
•M
•G
•The N assembles with the
polymerase and RNA in progeny
virus (spiral configuration)
•Virus exits by budding
•G protrudes from plasma membrane
•M binds to inner PM leaflet

5. •Animal susceptibility
•All warm-blooded animalscan be infected with varying
susceptibility
•High -wolves, coyotes, foxes, dogs
•Intermediate -skunks, raccoons, bats
•Low -opossums
•Virus occurs in saliva, nervous system, urine, lymph, milk
•Recovery is rare and only occurs in bats; fatal in nearly all others
•Vampire bats can transmit virus for months
Rabies Virus

6. Rabies Virus
•Pathogenesis
•Requires several weeks for infection to become apparent
•Transmission through bite or scratchfrom infected animal
•Replication in muscle and connective tissuesat site of
inoculation
•Enters peripheral nervous systemat neuromuscular
junctions
•Spreads up the peripheral nerves to the central nervous
system
•Encephalitis
•Virus grows to high titers in the salivary glands
•Rabies patients must be restrained
•Negri bodiesappear in neuron cell bodies
•Clinical spectrum
•Prodrome-nausea, headaches, fever, sore throat,
photophobia
•Acute neurologic phase -apprehension, nervousness,
hallucinations, behavioral anomalies, salivation,
perspiration, hydrophobia, photophobia
•Coma -seizures and death (99+%)
Negri bodies

7. Rabies Virus
•One survival using novel medical treatment
•NEJM. 2005. 352:2508-2514
•15 year old Jeanna Giese bitten by a bat
•Presented with clinical rabies after one month
•Treatment
•Induced coma
•Administered high doses of ketamineto suppress brain activity
•Required mechanical ventilation
•Administered heparin
•Administered ribavirin, an antiviral, to protect the heart from rabies-induced
cardiomyopathy
•Days 8-10 showed improvement in cardiovascular and neurological functions
•By day 23 she could sit up in bed, but neurological manifestations persisted
•Required prolonged physical therapy, but is continuing to recover
•This treatment failed for a Texas boy

8. Rabies Virus
•Laboratory diagnosis
•PCR
•Serology (IFA)
•Animal control
•Rabid or suspected rabid animals are killed and examined by
histopathology for Negri bodies and viral antigen
•Vaccination of pets is required by law in most states
•Immunity and protection
•Vaccines
•First one developed by Pasteurby using spinal cords from infected dogs
•Today’s principal vaccine is the human diploid cell vaccine(HDCV) made in
the WI-38 fibroblast cell line
•Virus is inactivated by βPL
•Post-exposure prophylaxis
•One dose of hyperimmune antiserum
•Five immunizationsover 28 days

9. •Epidemiology
•Enzooticin wild and domesticated animals
•In the U.S., edible vaccinesare dispersed to control wild animal rabies
•More than 200 people die from rabies in China each month
•Reservoirs might be bats
•But the slow-growing natureof rabies virus also contributes to its persistence
in nature
Rabies Virus

10. Prion Diseases
•Proteinacious infectiousagents
•Diseases are transmissible spongiform
encephalopathies(TSEs)
•There are also inheritedspongiform
encephalopathies
•Human
•Creutzfeldt-Jakob Disease-sporatic
•New Variant CJD-from beef (“mad cow disease”)
•Kuru -ritualistic cannibalism(consuming brains
of infected dead)
•Fatal familial insomnia
•Animal
•Bovine spongiform encephalopathy (“mad cow”
disease)
•Scrapie -sheep
•Chronic wasting disease-deer, elk, moose

11. Prion Diseases
•Pathogenesis
•Poorly understood
•The prion protein is a normal cellular protein, encoded by the
PRPCgene
•The gene is found on the short arm of chromosome 20
•It is thought to be involved inion transport
•It is prominently expressed in the CNS
•Some mutant alleles occur in familial enecphalopathies
•Protein folding
•The properly-foldedprotein is termed PrP
c
•The misfoldedprotein is termed PrP
Sc
•It is unknown why the protein misfolds
•However, once misfolded, it can cause misfolding of other copies
of PrP
c
•The misfolded protein is highly resistantto heat and protease
digestion
•TSEs have been transmitted by autoclaved surgical instruments
•The misfolded proteins apparently elude the ubiquitin/proteosome system
•Cells export the misfolded protein, which then forms extracellular plaques
•These plaques interfere with neuronal communication
Normal Misfolded