Rabies Virus Flashcards
History of Rabies Virus
** Rabies virus is the most _____ of all infectious diseases which infects all ____.
* Recognized in ____ before 2300 B.C. and in ancient ______
** Transmission of rabies was not recognized until ___
* In NA, rabies is most common in ?
** Present worldwide, with the exception of ?
* Lagos bat virus: Lyssavirus was initially isolated from ____ bats
Rhabdo means?
Rabies is an occupational disease. What does this mean?
lethal, mammals, Egypt, Greece, 1804
skunks, foxes,
raccoons, bats, dogs, and cats
Hawaii, Japan, Great
Britain, & smaller islands
fruit
rods
Means that contraction of this virus is related to your job.
General properties of Rhabdovirdae
Virion:
-** ________ with large _____
-** _____ shaped
-70 nm in diameter
-***** _______ coiled cylindrical nucleocapsid
Genome:
- ____(-____) sense RNA molecule
-11-15 Kb in length
- _______replication
Virus:
-VSV: cause rapid _____
-*Street rabies virus: non-_____
Viral RNA-dependant RNA polymerase
transcribes 5 subgenomic mRNA
translated into 5 proteins
1- L: RdRP
2- G: glycoprotein
3-NP: nuclotpotien
4- P: phosphoprotein
5: M: matrix protein
Enveloped, spikes, Bullet, Helically, ss, Ve, Cytoplasmic, cytopathology, cytopathogenic
Label the image accordingly
What is pictured here?
Bullet shaped rabies virus
Table is showing the comparison between different virus families.
Site of replication of Rhabdoviridae?
Virion morphology?
Mode of transcription?
Host range?
Pathogenic potential?
Cytoplasm
Bullet shaped
Rhabdoviridae has a ____ host range.
wide
- Rhabdoviridae has how many subfamilies? Name each subfamily.
- Name the genuses within Rhabdoviridae?
- Name the most important viruses within the genus Lyssavirus?
- 3 subfamilies: Alpha, Beta, Gamma
- Ephemerovirus, Lyssavirus, Vesiculovirus.
- Rabies, Lagos bat
Lyssavirus: lethal viruses affecting ______ and _______ in Central and south America
Novirhabdovirus: affects _____
dogs, cattle, fish
Genome runs from?
Key genes?
It is a negative sense virus, therefore?
Examples of Vesi, Lyssa, Ephem?
3’ o 5’
M. P, N, G
It needs to undergo transcription and then translation
Explain how rhabdoviridae replicates
Virus attaches to receptors, enters lysosomes, ph drops, acidification occurs, nucleic acids released, cytop?, two events: cutting of viral genome or cutting of viral proteins
Assemble virions into cell membrane –> cell membrane –> go to another cell.
Rabies virus/Transmission
– Zoonotic disease
* Reservoir: ___ animals
* Vector: ___ animals and _______ dogs and cats
* Source of virus:
**– Major: _____ in _____ of a rabid animal
**– Minor: _____ in ___ _____ containing rabid bats
* At risk people:
– _______ and animal ______
– _____ bitten by a rabid animal
– Inhabitants of countries with no pet _____ program
** ___ incidence of human illness
** Chance of infection when handling ______ tissues
– Biosafety level __
– Personal ______ equipment
* Rarely causes ____ formation
wild, wild, unvaccinated, saliva, bite, aerosols, bat caves, Veterinarians, handlers, Person, vaccination, Low, contaminated, 3, protective, vesicle
Broad picture of Rabies virus (RABV) across the globe
Two important epidemiological cycles are recognized:
1. Canine (______) rabies :involves ___ dogs and accounts for more than ____% of human cases in _______ countries.
- Sylvatic rabies: involves a range of _____ species, principally small to mediumsized ______, that varies geographically and includes ?
- In North America which species act as important reservoirs?
- Rabies - ______ perivascular cuffing and ______ inclusions
_____ bodies - found most consistently in the _______ cells of the _____, but are not detectable in many cases.
urban, stray, 95, developing, wildlife, carnivores, foxes, coyotes, racoons, skunks, jackals, mongooses and bats.
racoons, skunks, foxes and bats
lymphoid, intracytoplasmic, Negri, pyramidal, hippocampus
Describe the pathogenesis of rabies
Rabies pathogenesis:
- Raccoon bitten by rabid animal
- Rabies virus enters through infected saliva
- Raccoon bites a dog or cat
- Dog or cat come in close contact with human —> bite
- Cycle begins again
Describe the pathogenesis of Rabies
Once bitten, canine species puncture skin, virus contaminates site of bite —> transmits through nerve —> CNS
How does rabies reach the CNS?
Rabies moves in nerve tissue, NOT the blood.
RABV/Disease Mechanisms
* Rabies affects only _____-blooded animals with ____.
* People are also mammals
* Birds, snakes, and fish are not mammals
* Rabies is usually transmitted in ____ and is acquired from the bite of a ____ animal
* Virus is not very ____ and seems to remain __-associated
* Virus replicates in the _____ at the ___ of the bite with minimal
or no symptoms
*** The rabies virus incubation period depends on:
-The infectious ____ and
-The proximity of the infection site to the ____ and ____
- ____ of the virus
-Host ____
warm, fur, saliva, rabid, cytolytic, cell, muscle, site, dose, CNS, brain, immunity
Describe the incubation period of Animal and human rabies.
- Animal rabies: varies from a few weeks to a few years but typically (1-3 months)
- Human rabies: usually 3-8 weeks, rarely as few as 9 days, may be as many as 7 years.
Closer to the CNS = shorter incubation period.
Define street virus. What is the source of street virus?
Define fixed virus. What is the source of fixed virus?
Rabies infection results in?
The greater the virus particle, the shorter the incubation period.
Pathogenesis of RABV
* Infection through animal ___
*** Replication in the _____: virus binds to the _______ ______ receptors
on ______ membranes at the ____
* _______ axonal transport
* _____ dissemination
* Centrifugal spread along _____& _____ nerves
bites, muscles, nicotinic acetylcholine, postsynaptic, NMJ, Retrograde, CNS, sensory, autonomic
Pathogenesis of RABV
Raccoon bites dog –> transmits rabies through bite –> virus travels to muscle –> regional (motor) nerves –> spinal chord –> brain –> virus shed in salivary gland of infected animal
RABV replication and spread through nerves
1. Define anterograde and retrograde infection.
2. Rabies virus and pseudorabies
cross the synaptic ___
- Anterograde neuronal: spread
from the neuron cell body
toward the axon terminus) - Retrograde infection : spread of
virus from the axon terminals to
the neuronal cell body and is
directionally opposite to
movement of the nerve impulse
junctions
Animal RABV Clinical disease
After the bite of a rabid animal
–> Two clinical forms of the disease:
1. Describe what happens to an infected animal suffering from Furious rabies.
2. Describe what happens to an infected animal suffering from Dumb (or paralytic) rabies.
3. Describe other signs and symptoms associated with rabies infection.
4. In terminal cases, what does rabies infection result in?
- Animal becomes restless, nervous, aggressive, and dangerous
Loses fear of humans and bites at anything that gains its attention. - dysfunction could be a dominant symptom. The animal cannot swallow water because of pharyngeal paralysis,
giving rise to “hydrophobia.” = animal unable to drink water. - Other signs include excessive salivation, exaggerated responses to
light and sound, and *hyperesthesia(
* As the encephalitis progresses, fury gives way to paralysis, and the
animal presents the same clinical picture as seen in the dumb form.
- Other signs include excessive salivation, exaggerated responses to
- Terminally:
-Convulsive seizures, coma, & respiratory arrest
-** Death occurring 2–14 days after the onset of clinical signs
RABV is suspected If any animal is acting _______????
General sickness
* Problems _____
* Lots of ___ or saliva
* An animal that bites at ________, aka ?
* An animal that appears _____ than you would expect
* An animal that’s having trouble ____ or may even be ______
* A bat that is on the ____
strangely, swallowing, drool, everything, pica, tamer, moving, paralyzed, ground
Human RABV
RABV infection ____, which usually progresses over ___-___ days
* After weeks to months, the virus
infects the ____ nerves and
travels up the CNS to the brain
(______ phase) (__-__ days) resulting in?
apprehension, anxiety, agitation,
irritability, insomnia and depression
* Infection of the brain causes classic
symptoms, coma, and death
(neurologic phase)
Disorientation and hallucinations;
paralysis; episodes of terror and
excitement;
Hydrophobia; hyperventilation;
hypersalivation; and seizures.
* These symptoms are invariably
followed by coma and death
fatal, 2 – 21, peripheral, prodrome, 2-10
- If there is a large amount of viruses in nervous tissue, what does that means?
- What is Guillan-Barre syndome?
- As long as there is a large amount of virus in nervous tissue, virus will be shed in saliva.
- Fatal autoimmune disease reported after rabies virus vaccine administration.
- Name the areas of the brain suitable for RABV testing.
- Samples should not be _____
but _______ - Large animals: only submit the _____
- Bats: try not to crush the animal
especially the ____ - Small animals: submit the _____
animal
- Midbrain, Medulla Pons, Brain stem, Hippocampal neurons
- frozen, refrigerated, head, head, whole
Label the images accordingly.
What part of the brain do we specifically want to sample when testing for rabies virus?
RABV laboratory diagnosis
1. Occurrence of neurologic symptoms in a person who has been bitten by an animal, it is….?
2. Diagnosis occurs?
*3. Describe the diagnostic methods?
*4. Histologically, what can you see in an animal infected with rabies?
5. How can you detect the rabies antigen, antibody?
6. What establishes a rabies diagnosis?
- too late
- postmortem
- Microscopical, virological, & serologicalmethod
- Aggregates of viral nucleocapsids (Negri bodies) in Purkinje cells hippocampus in the brain
- Direct immunofluorescence IFTA
* ELISA
* IHC: detection of viral Ag in the neurons
- Direct immunofluorescence IFTA
- The detection of rabies antigen, antibody, viral RNA, or the isolation of virus establishes a diagnosis of rabies.
-Eosinophilic, sharply outlined,
-Pathognomonic inclusion bodies
-2–10 μm in diameter
-Found in the cytoplasm of certain nerve
cells containing the virus of rabies,
especially in pyramidal cells of the
hippocampus.
What can be seen in this image?
Perivascular cuffing or inflammation around a blood vessel. Brown = rabies virus
Bit by rabid animal
* If animal is healthy and owner does not want to euthanize:
* Quarantine for ____ days
* If animal become ill, what are your options as the owner?
- 10
- -Euthanize
-Submit for testing
-Precautions when removing the head
-Keep chilled not frozen
RABV/Treatment & Prophylaxis
* Clinical rabies is almost always _____ unless ____
* Only hope:
– Post exposure ________
– Used only for people exposed by ___ or by contamination of an ____ wound or ____ membrane to the ____ or ____ tissue of an animal suspected to
be infected with the virus
– A rabies ________ ______ is essentially an estimation of an immune response against rabies virus (either through exposure or vaccination
* Antibody ______ at the late stages
* Antibody can block the progression of the virus
* The long IP allows active immunization as a postexposure treatment
fatal, treated, prophylaxis, bite, open, mucous, saliva, brain, antibody titer, response
Clinical applications of the rabies virus Abs
* The Purpose of Rabies Primary or Pre-exposure Vaccination:
- Those who work in professions at higher risk for rabies exposure,
such as veterinarians, animal handlers, and certain laboratory workers
1. A series of _____ rabies vaccines to be considered ___-exposure vaccination in case they
are ever exposed to rabies
* Pre-exposure prophylaxis is administered for several reasons
- If a person undergoes the pre-exposure series, it eliminates the need for Rabies Immune
Globulin (RIG)
* RIG is ONLY given to those who have NEVER received rabies vaccinations
* Administering RIG to those who have been previously vaccinated may interfere with
that person’s response to booster vaccines
**** Rabies Pre-exposure Vaccination Schedule
** Three 1.0-mL injections of either a human diploid cell-based (Imovax®) or a purified
chick embryo-based (RabAvert®) vaccine should be administered intramuscularly
(deltoid area)
* One injection per day on days 0, 7, and 21 or 28
* Titer Schedule
* Two working guidelines
three, pre
Clinical applications of the rabies virus Abs cont….
** Recommended “cut-offs”: the rabies Ab titer in which rabies vaccinated
individual should receive a _____ dose
* Rapid Fluorescent Focus Inhibition Test (RFFIT) was performed in cell culture
to determine the rabies virus neutralizing antibody level in human or animal sera
RFFIT used as an indicator of rabies virus replication
** Two systems:
** 1- The advisory committee on Immunization Practices (ACIP): titer less than
1:5 dilution by RFFIT should receive a booster dose
** 2. WHO: titers of ≥0.5 IU/mL are considered adequate for rabies protection
* If the level falls below this value, a booster dose of the rabies vaccine may be
recommended for people at frequent risk of rabies virus exposure
booster
Types of RABV Vaccines
1. Inactivated whole virus vaccines are available for humans
– Nervous Tissue Preparations: associated with rare complication of demyelinating allergic encephalitis
– **Duck Embryo Vaccine : grown in embryonated ____ eggs
Vaccine has a lower risk of ____ _____ but less immunogenic.
– **Human Diploid Cell Vaccine (HDCV):
– Currently ____ vaccine available
– Efficacy rate of nearly ____%
– ______ any severe reactions.
– Very ____
– **Other Cell culture Vaccines - because of the _____ of HDCV, other cell
culture vaccines are being developed for developing countries.
– Recent data suggests that reduced dose of HDCV given ______ may be
effective
**Type: ______ (___) viral vaccine
**Dose: 2.5 ml S/C vaccine ad mistered into the abdominal wall
***EX: Vaccinia poxvirus rabies vaccine by introducing ___ protein of rabies into
vaccinia virus: used as ____ ____ vaccine administered to wild carnivores distributed
by dropping from aircrafts
duck, allergic encephalitis, best, 100, Rarely, expensive, expense, intradermal, inactivated (killed), G, oral bait
2- Vesicular stomatitis virus- VSV
* 1982-83: Outbreak in _____ U.S.
– Previously, epizootic waves typical
– Now an _____ occurrence in U.S.
* Western hemisphere
– North, Central, and South America
* Emergence in eastern hemisphere?
– 2009: Bahrain, Laos (suspected)
– 2009: Pakistan (limited regions)
* Southwest U.S.
– Outbreaks in warmer regions
* Southeast U.S.: enzootic cycle
Stomatitis: inflammation of the oral mucosa
western, annual
Animal transmission
VSV Vectors?
Mode of transmission?
Human transmission
Mode of transmission?
Sandflies, blackflies, seasonal outbreaks.
Infected animals, contaminated objects
Direct contact: infected tissues, vesicular fluid, saliva, insect bites (blackfly, sand-fly), aerosol (lab settings).
Hosts:
Wildlife: ?
(3) –> humans
Dynamic exchange between wildlife, mosquitos, domestic species.
Deer, bats, rodents, Cattle, pigs, horses
Pathogenesis of VSV
** - Virus can be transmitted (________) by arthropods including?
–> Transmission steps:
1. Virus enters body through ____ in skin and ____.
2. Virus can be transmitted through _____ (food, milking machines, restraint devices, etc)
* The incubation period is ?
* VSV causes local ______, epithelial _______, and
interstitial ______.
* There is no _______ viremic phase of the disease.
* Virus spreads by ______ of the lesion such that the
entire epithelium of tongue or teats can slough off.
* There are very high titers of the virus during the first few days.
mechanically, (Sandflies, mosquitoes, black flies, midges, and houseflies).
breaks, mucosa, fomites
1 to 5 days, vesiculation, denudation, edema, systemic, extension
Clinical features of VSV
Fever and excessive salivation are the first signs in
cattle and horses
Lameness is the first sign in pigs.
** Vesicular lesions are observed in the ?
** _______, _______, and _____ of suckling calf in cattle.
In horses, tongue lesions are most pronounced resulting
in sloughing of epithelium.
In swine, vesicular lesions in snout & coronary band.
Lesions heal in 7 to 10 days
Morbidity
**– Range: __-___%
– Most animals seroconvert
*Mortality
– Higher in adults
– Death rare in cattle and horses
tongue, oral mucosa, teats, and coronary bands.
Anorexia, lameness & rejection of suckling , 5 to 90
VSV-Clinical Signs
* Incubation period: 3 to 5 days
* Fever and vesicles that
resemble FMD
* – _____ lesions
**** Clinical signs: ?
– Coronary band lesions
*****Effects which species?
– Vesicular lesions
* Oral, mammary gland,
coronary band,
interdigital region
– Usually isolated to one
body area
**–
* Recover within 2 weeks
Oral
Drooling, chomping, mouth rubbing, lameness, Salivation, lameness
Cattle, pigs
Study species
What to know from here:
Bottom left box
All the fish rhabdoviruses are now placed in two genera. Name these tow genera:
- Novirhabdovirus
- Vesiculovirus
Which scientist discovered the first retrovirus?
Retro means?
Retro is derived from?
Retroviridase has how many subfamilies, genera, and species?
Francis Peyton Rous
Reverse backward.
Derived from thee reverse transcriptase (RNA-dependent DNA polymerase) found in virions of all members of the family.
2,11,68
What are the names of the subfamilies of Retroviridae?
Orthoretrovirinae, Spumaretrovirinae
What type of virus is pictured? label accordingly
What type of virus is pictured?
Retrovirus
POL = polymerase
GAG = protein
ENV =
What type of virus is pictured? Label accordingly.
The innermost portion of the virion contains the?
Describe the morphology of the capsid?
Is this virus enveloped?
Is this virus haploid of diplod?
Genome
Icosahedral
Enveloped
Diplod, a dimer of linear +Ve sense stranded RNA
Standard genome structure
The genus Lentivirus has which virus affecting cats?
The genus Gammaretrovirus has which virus affecting cats?
The genus, lentivirus, usually causes?
FIV
FeLV
Immunodeficiency
- Mature virus enters cell
Virus affects immune cell, triggering immunosuppression.
Retrovirus replication Cycle
* The lifecycle of a typical retrovirus starts with the interaction between viral ______ protein (Env) and cellular ______.
* This induces membrane ______ and entry of the viral _____.
* The viral genomic RNA (gRNA) is reverse-transcribed into cDNA using a viral _____ _______ and a packaged cellular ______ as the primer.
* The viral cDNA enters the nucleus in the form of a ___-________ ______ and is inserted into the host genome.
* The DNA provirus is transcribed by host machinery to produce new ______ that are packaged or serve as mRNAs (full-length and spliced variants) that are
translated to generate viral proteins.
* The viral ____ and ___-____ polyproteins drive viral ______ at the plasma membrane; during this process, viral ______ and some ____ factors, including the _____ primer, are recruited. The newly budded virion undergoes maturation to become fully infectious. Retrovirus replication cycle.
envelope, receptors, fusion, capsid, reverse transcriptase (RT), tRNA, pre-integration complex, gRNAs, Gag, Gag-Pol, assembly, gRNA, host, tRNA
Describe the difference between a latent and active HIV infection.
- Latent: After HIV enters host cells, integrates itself into host genome and remains inactive until ideal conditions arise for it to become activated.
- Active: In case of HIV, under stress or other conditions, virus is activated –> replicates –> active infection.
Don’t study
Describe retrovirus induced oncogenesis.
From parent to offspring via ova or sperm to newly hatched chicks. Very important to choose chick wisely.
What disease causes this?
Jaagsiekte sheep retrovirus (JSRV) of sheep
Ovine Pulmonary Adenocarcinoma (OPA)
Big knee or Caprine Retrovirus
What disease is pictured here?
ENTC
What disease is pictured here?
Mouse mammary tumor virus MMTV
* MMTV: tumor in the mammary gland of the
mouse
no slide
Describe the pathogenesis of FIV
CD8+ is a marker because host tries to compromise by MHC-I.
Emailed Hemida about this
Drop in lymphocytes (lymphopenia)
Bottom right
