Rabies Virus Flashcards
(112 cards)
1
Q
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?
A
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.
2
Q
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
A
Enveloped, spikes, Bullet, Helically, ss, Ve, Cytoplasmic, cytopathology, cytopathogenic
3
Q
Label the image accordingly
A
4
Q
What is pictured here?
A
Bullet shaped rabies virus
5
Q
Table is showing the comparison between different virus families.
Site of replication of Rhabdoviridae?
Virion morphology?
Mode of transcription?
Host range?
Pathogenic potential?
A
Cytoplasm
Bullet shaped
6
Q
Rhabdoviridae has a ____ host range.
A
wide
7
Q
- Rhabdoviridae has how many subfamilies? Name each subfamily.
- Name the genuses within Rhabdoviridae?
- Name the most important viruses within the genus Lyssavirus?
A
- 3 subfamilies: Alpha, Beta, Gamma
- Ephemerovirus, Lyssavirus, Vesiculovirus.
- Rabies, Lagos bat
8
Q
Lyssavirus: lethal viruses affecting ______ and _______ in Central and south America
Novirhabdovirus: affects _____
A
dogs, cattle, fish
9
Q
Genome runs from?
Key genes?
It is a negative sense virus, therefore?
Examples of Vesi, Lyssa, Ephem?
A
3’ o 5’
M. P, N, G
It needs to undergo transcription and then translation
10
Q
Explain how rhabdoviridae replicates
A
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.
11
Q
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
A
wild, wild, unvaccinated, saliva, bite, aerosols, bat caves, Veterinarians, handlers, Person, vaccination, Low, contaminated, 3, protective, vesicle
12
Q
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.
A
urban, stray, 95, developing, wildlife, carnivores, foxes, coyotes, racoons, skunks, jackals, mongooses and bats.
racoons, skunks, foxes and bats
lymphoid, intracytoplasmic, Negri, pyramidal, hippocampus
13
Q
Describe the pathogenesis of rabies
A
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
14
Q
Describe the pathogenesis of Rabies
A
Once bitten, canine species puncture skin, virus contaminates site of bite —> transmits through nerve —> CNS
15
Q
How does rabies reach the CNS?
A
Rabies moves in nerve tissue, NOT the blood.
16
Q
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 ____
A
warm, fur, saliva, rabid, cytolytic, cell, muscle, site, dose, CNS, brain, immunity
17
Q
Describe the incubation period of Animal and human rabies.
A
- 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.
18
Q
A
19
Q
Define street virus. What is the source of street virus?
Define fixed virus. What is the source of fixed virus?
Rabies infection results in?
A
The greater the virus particle, the shorter the incubation period.
20
Q
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
A
bites, muscles, nicotinic acetylcholine, postsynaptic, NMJ, Retrograde, CNS, sensory, autonomic
21
Q
Pathogenesis of RABV
A
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
22
Q
RABV replication and spread through nerves
1. Define anterograde and retrograde infection.
2. Rabies virus and pseudorabies
cross the synaptic ___
A
- 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
23
Q
A
24
Q
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?
A
- 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
25
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
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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
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1. If there is a large amount of viruses in nervous tissue, what does that means?
2. What is Guillan-Barre syndome?
1. As long as there is a large amount of virus in nervous tissue, virus will be shed in saliva.
2. Fatal autoimmune disease reported after rabies virus vaccine administration.
28
1. 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
1. Midbrain, Medulla Pons, Brain stem, *Hippocampal neurons*
2. frozen, refrigerated, head, head, whole
29
Label the images accordingly.
What part of the brain do we specifically want to sample when testing for rabies virus?
30
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?
1. too late
2. postmortem
3. Microscopical, virological, & serologicalmethod
4. Aggregates of viral nucleocapsids (Negri bodies) in Purkinje cells hippocampus in the brain
5. * Direct immunofluorescence IFTA
* ELISA
* IHC: detection of viral Ag in the neurons
6. The detection of rabies antigen, antibody, viral RNA, or the isolation of virus establishes a diagnosis of rabies.
31
-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.
32
What can be seen in this image?
Perivascular cuffing or inflammation around a blood vessel. Brown = rabies virus
33
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?
1. 10
2. -Euthanize
-Submit for testing
-Precautions when removing the head
-Keep chilled not frozen
34
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
35
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
36
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
37
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
38
39
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
40
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).
41
Hosts:
Wildlife: ?
(3) --> humans
Dynamic exchange between wildlife, mosquitos, domestic species.
Deer, bats, rodents, Cattle, pigs, horses
42
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
43
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
44
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
45
Study species
46
VSV-Laboratory diagnosis
* Before collecting or sending any samples, the proper ______ should be notified
* Samples should only be sent under _____ conditions and to _____ laboratories to prevent the spread of the disease.
* Virus ______
* Viral ______ detection
– Using vesicular ___ or _____
– Tests to perform:
* Antibody tests
– Using Paired ____ samples
– Tests to perform:
authorities, secure, authorized, isolation, antigen, fluid, epithelium
ELISA, complement fixation,
virus neutralization
serum
ELISA, complement fixation, virus neutralization
47
What to know from here:
Bottom left box
48
Bovine ephemeral fever virus (BEFV) is called _____-day sickness, meaning it is always ___ days and usually recover after.
Bovine epizootic fever of japan.
* The name ephemeral fever was applied very ___ in the disease’s recorded history
* Ephemeral lasting for a very ___ time
* The disease is not ephemeral in the sense of being hard to see
* ___ day sickness
* Clinical signs generally persist for about ___ days then disappear ______ with _____ recovery
* A non contagious epizootic
* Arthropod-born viral disease
* Affect cattle and water buffaloes
* Characterized by; sudden onset of fever, depression stiffness,lameness, and
rapid recovery.
Three, three, early, short, 3 , three, suddenly, complete
49
BEFV-Incubation period
* IP varies between __ and __ days, and ___ days is the rare extreme
*The _____ is probably influenced by; the ____ and ____ used
*The natural incubation period can only be inferred but is probably similar
* ____ age groups of cattle are susceptible but the disease is more common in age
group of __-___ months.
* In apparent infections may occur in some wild ruminants
* Sheep, goats, and other animals are not known to become infected
2, 4, 9, time, strain, dose, All, 6-24
50
BEFV-Transmission
* In nature, Only by ____ bite: _______-Mosquitoes.
* The disease will not spread from cow to cow by; close contact,
droplet infection, bodily excretions
or by the transfer or injection of exudates.
* Experimental evidence that BEF virus is not spread by semen.
*Meat does not represent even a theoretical risk for transmission:
virus is rapidly inactivated at pH levels below 5, such acidic
levels are attained rapidly in bovine muscle after death
Insect, Culicoid
51
BEFV clinical signs
Morbidity : may reach to 30%
* Mortality: Low
* Fever: (40-41.5C (105-107 F) with biphasic
or tri-phasic fever spaced 12-18 hrs.)
* Discharge from the eyes
* Discharge from the nose
* Muscle tremors, temporary _____
* ____ down(3days) ____ limbs outstretched- to relieve muscle ____
* May lead to coma and death
--> Diagnosis based on:
* ____ of the infection
* _____ signs
* ____ diagnosis
* _____
* ______ of the virus
* Detection of viral ____
* Detection of antibodies by
_______
* _____
lameness, Lying, hind, cramp, History, Clinical, Laboratory, Sampling, Isolation, RNA, ELISA, Seroconversion
52
All the fish rhabdoviruses are now placed in two genera. Name these tow genera:
1. Novirhabdovirus
2. Vesiculovirus
53
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
54
What are the names of the subfamilies of Retroviridae?
Orthoretrovirinae, Spumaretrovirinae
55
What type of virus is pictured? label accordingly
56
What type of virus is pictured?
Retrovirus
POL = polymerase
GAG = protein
ENV =
57
What type of virus is pictured? Label accordingly.
58
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
59
Functions of some Retroviruses proteins
* The envelope surrounds an icosahedral capsid
* The capsid contains two ____, _____-sense, ____
strands of RNA
* Unique in possessing a reverse transcriptase (RNA-
dependent DNA polymerase)
* Double-stranded DNA is inserted as a provirus into the
host genome
--> Unique criteria of retrovirus genome:
* It is the only diploid genome (inverted dimer of two RNA
molecules)
* It is the only positive-sense, single-stranded RNA genome
that does not serve as _____ soon after infection
* It is the only genome to encode a _______ _________.
* It is the only viral RNA that is ______ and _______
by ____ cell mRNA-processing machinery
linear, positive, single, mRNA, reverse transcriptase, synthesized, processed, host
60
A. The GAG (____ _____ ____) gene encodes internal _____ proteins
B. The PRO (protease) gene
encodes the enzyme ____
C. The POL (polymerase) gene
encodes the enzymes?
D. The env (envelope) gene
encodes ____ (SU) and ____ (TM) _____ glycoproteins
Most likely to be expressed on the surface of a retrovirus
group specific ,antigen, structural, protease, reverse transcriptase and
integrase, surface, transmembrane, envelope
61
Standard genome structure
62
The genus Lentivirus has which virus affecting cats?
The genus Gammaretrovirus has which virus affecting cats?
The genus, lentivirus, usually causes?
FIV
FeLV
Immunodeficiency
63
Biological Properties of Retroviruses cont...
* Ability of retrovirus to ___ and ___
host-derived genetic sequences
* Ability of retrovirus to integrate into the host-cell ____
* Activation or inactivation of ___ genes near the ______ sites
* Ability to undergo _____ and _______
* Retrovirus can be used as vector to ____ some genes
* Retrovirus may induce _______
or ______ mediated diseases
acquire, alter, genome, specific, integration, mutation, recombination, deliver, immunosuppression, immune
64
Mechanism of viral DNA into the host DNA
Retroviruses are often ______. This is accomplished in 3 basic ways:
1. ______ of the provirus upstream of an oncogene. The viral long terminal repeat or LTR causes transcriptional ______ of the oncogene. The ____ of tumors is usually very ____.
2. _______ retroviruses arise that cannot _____ but have picked up an _____ from the host cell. The defective virus is propagated using functions of a co-infecting
replication-competent virus. These defective viruses are highly
Oncogenic, and tumors usually arise very ____.
3. _______ _______ _____ in, or carry a viral gene that interferes with, cellular genes that control host cell _____ (like tumor suppressor genes)
oncogenic, Integration, upregulation, onset, slow, Defective, replicate, oncogene, quickly, Retroviral genomes integrate, transcription
65
1. Mature virus enters cell
66
Endogenous retroviruses occur widely among vertebrates
* Proviruses that become integrated into the chromosomes of germ cells can be passed down
vertically via the sperm or egg DNA
Class I-ERV _____-related
Class II-ERV _____-related
Class III -ERV ______-related
* They are transmitted only as ____ in germ cell DNA from parent to offspring
* They are regulated by cellular genes and are usually ____
* They can be activated by ______, ______ or ______ with the production of new virions
* Once integrated into the germline, endogenous retroviruses tend to proliferate
Endogenous retroviruses (ERV)
provirus, silent, irradiation, mutagens, carcinogensGamma, Beta, Spuma
67
Virus affects immune cell, triggering immunosuppression.
68
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
69
Describe the difference between a latent and active HIV infection.
1. Latent: After HIV enters host cells, integrates itself into host genome and remains inactive until ideal conditions arise for it to become activated.
2. Active: In case of HIV, under stress or other conditions, virus is activated --> replicates --> active infection.
70
Don't study
71
Describe retrovirus induced oncogenesis.
From parent to offspring via ova or sperm to newly hatched chicks. Very important to choose chick wisely.
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Horizontal and Vertical Transmission of ALV
A. Affected birds become inappetent,
weak and emaciated
B. They have pale wattles and the liver
and Bursa of Fabricius may be
enlarged
C. Osteopetrosis sometimes accompanies
lymphoid leukosis
D. Subclinical infections of ALV are
associated with low egg production and
fertility
did not have this slide
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Alpharetrovirus
Avian leukosis/sarcoma complex- (ALV)
* Caused by certain members of _______/_______ group of avian retroviruses and commonly called avian leukosis viruses and belongs to subgroups ?
* Diseases include: ?
* Chickens are the natural hosts for all viruses of the leukosis/sarcoma group
* Transmission: ______ transmission (eggs), _______ transmission and by feces (chicken to chicken)
* It affects chickens worldwide, with susceptibility varying considerably among different strains and types of stock - egg layers are generally more susceptible to lymphoid leucosis
* Virus, disease syndrome and viral oncogene
* A. ALV- erythroblastosis – ?
* B. RSV – sarcoma – ?
* C. Avian myeloblastosis virus – myeloblastosis – ?
leukosis, sarcoma, A, B, C, D, E and J
- lymphoid leukosis - myeloblastosis
-erythroblastosis -osteopetrosis
-myxosarcomas -fibrosarcomas
Vertical, Horizontal, c-erbB gene, v-src, v-myb
74
Clinical signs, PM lesions and Control-ALV
* Depression, Emaciation
* Loss of weight
* Persistent low mortality
* Enlargement of abdomen, liver or bursa
Focal ____ to _____ tumors, initially in the primary immune organs (name these). The _____, may be very large.
Microscopic - cells lymphoplastic
Eradication of ALSV by establishing breeder flocks that are free of exogenous ALSV
Differential diagnosis of ALV
-Egg drop syndrome virus
-Marek’s disease virus
-Fowlpox virus
-Chicken anemia virus
grey, white, bursa, liver, spleen, kidney, and heart, liver
75
Deltaretrovirus
Bovine Leukemia Virus-BLV
* Viral disease of ____ cattle : neoplasia of ________ and ______ ______
* The prevalence in a herd may be _____, but only a few animals develop fatal ________
* Spread by contact with contaminated _____ from an infected animal (tagging,
dehorning, tattooing, multiple animal needle use and rectal palpation)
* Most infections (90%) take place _____ in the life of a calf when virus
transmitted in the _____.
adult, lymphocytes, lymph nodes, high, lymphosarcoma, blood, early, milk
76
Bovine Leukemia Virus-BLV
BLV : usually seen in animals ___months and older
* Disease evolves slowly, taking several _____ or _____ to develop
* No clinical signs during the ______ infection, however, adult animals may exhibit any of the following symptoms:
* _______ heart failure
* _________ milk production
* __________ due to neuronal involvement
* __________ weight loss
* recurring ____
* _______
* Affected cattle, enlargement of ____ lymph nodes is an outstanding symptom
* Palpable lumps found in the _____, in the front of the ________, and behind the _____.
18, months, years, initial, congestive, decreased, paralysis, progressive, bloat, weakness, all, neck, shoulder, udder
77
Bovine Leukemia Virus-BLV
Animals that do develop disease, clinical signs are seen at __ to ___ years of age
* Lymphoid tumors in ?
* BLV should be suspected in _____ cows with enlarged ______ lymph nodes
4, 8, lymph nodes, heart, spleen, kidneys, uterus, spinal meninges, and brain, older, external
78
Pathogenesis-Diagnosis and control- BLV
Oncogenesis : integration of a bovine proviral __-_____ gene(s) into cellular DNA
Major target cells are __ lymphocytes
Animal destined to develop disease, infection at first inapparent, then may
progress to a persistent lymphocytosis, and finally to ______
Enlarged lymph nodes & leukemic infiltrations into a variety of organs and tissue
Diagnosis: detection of BLV ______ in the ____ and/or ___
No treatment or vaccine that will prevent infection.
Pasteurizing or freezing colostrum or milk destroys BLV infectivity__
v-onc, B, neoplasia, antibodies, blood, milk
79
Visna Maedi or Ovine Progressive pneumonia (OPP)
* Wasting (_____) and dyspnea (____)
* ________, ____-acting, ______ diseases of sheep worldwide
* Associated with thin ___ syndrome
* ____ _____ (______): firm enlarged udder with no milk
* Results from an accumulation of fibrous tissue in
* the udder
* _____ ____ mechanism for the spread of visna virus in ____
* Nanoparticles are internalized within cells and then release high levels of toxic ions, has been proposed
* as a behavior in the cellular uptake of Ag nanoparticles (AgNPs)
Visna, Maedi, Incurable, slow, wasting, ewe, Hard bag, lungers, Trojan Horse, monocytes
80
Jaagsiekte sheep retrovirus (JSRV) of sheep
Ovine Pulmonary Adenocarcinoma (OPA)
* The causative agent of contagious ____ cancer in sheep called ovine pulmonary _________ (OPA)
* ‘jaagsiekte’, meaning ____ (=jaagt) sickness (=ziekte)
* JSRV-induced tumors arise from epithelial cells
in the lower airway, and tumor cells express
markers of type ____ ________/ alveolar and/or bronchiolar epithelial cells
lung, adenocarcinoma, driving, II, pneumocytes
81
What disease causes this?
Jaagsiekte sheep retrovirus (JSRV) of sheep
Ovine Pulmonary Adenocarcinoma (OPA)
82
Caprine Arthritis-Encephalomyelitis (CAE) OR ____ _____ or Caprine ______
* Genetically related to OPP virus but distinct, this is one of the most ______ diseases of goats in the United States and worldwide
* CAE: List the five main clinical signs.
* Primary transmission through colostrum and milk
* A. It is caused by persistent infection with ______ ______ _______ virus (CAEV), a lentivirus
* B. It is characterized by _______ in adult goats and ___________ in kids
* C. Kids are usually infected with the virus through ingestion of ________ or milk from infected ___
* D. Swelling of affected joints (especially ____), reduced ___ production, a rapid progressive ______ disease (< 4 months of
age) with posterior paresis to quadriplegia.
Big knee , retrovirus, common
Arthritis, mastitis, encephalitis, interstitial pneumonia, and progressive weight loss, caprine arthritis-encephalitis, polyarthritis, encephalomyelitis, colostrum, does, carpus, milk, neurological
83
Big knee or Caprine Retrovirus
84
Enzootic nasal tumor virus in sheep (ENTV)
Enzootic nasal adenocarcinoma (ENA) Sugar
* Similar to the ______ virus (ovine pulmonary carcinoma)
* ________ or ______
* May invade sinus/adjacent bony structure
* Usually arises from ethmoid mucosa
* Rarely ______
* Death due to ______ and weight ____
Jaagsiekte, Bilateral, unilateral, metastasis, anorexia, loss
85
What disease is pictured here?
ENTC
86
What disease is pictured here?
Mouse mammary tumor virus MMTV
* MMTV: tumor in the mammary gland of the
mouse
87
Lentivirus
Equine infectious anemia (EIAV)
* EIA: (Swamp Fever), affect members of Equidae, including horses, mules and donkeys
* EIAV: Infect horses for life, producing intermittent attacks of illness (during which the horse may die) followed by periods during which the horse may
appear normal
* EIAV : spread mechanically. blood containing virus has to be transmitted from an infected horse to a susceptible horse by a vector, such as an insect, infected syringes, needles or surgical equipment
* EIAV : cross the _______ barrier and cause fetal infection & a _______ stallion can infect
healthy mares during breeding
* EIAV diagnosed in many areas of the ____ & infection exist ______
placental, symptomatic, world, worldwide
88
Lentivirus
Synonyms
* ____ Fever,
* ______ Fever,
* ____ Fever,
* ______ ______ Fever,
* ______ Disease
Swamp, Mountain, Slow, Equine Malarial, Coggins
89
Transmission of EIAV
* Only takes ____ drop of blood
* _____ bites: blood-feeding flies such as (horseflies, stable flies, and deer
flies)
*** _______ are not capable of transmission of EIAV
* Mechanical/lateral transmission
-hoof knives
-needles (tattooing or blood collection )
-Dirty syringes and instruments
-Blood transfusion
-Intrauterine
one, Insect, Mosquitoes
90
Mechanism of EIAV persistence
* EIAV incorporated its genomic code into the ________ DNA
* EIAV can reproduce in the __________
* Viral ___________ kills macrophages
* ______ state is eventually achieved with very low virus counts
* EIAV infection can go dormant for _________ period or ________.
macrophage, macrophages, reproduction, Steady, prolonged, lifetime
91
EIAV -Clinical Sings
Three clinical forms/stages of EIAV
*** Acute/ Sub acute form:
responses generally occur __-___ days after initial exposure
*Horses may develop _____, go off _____, or ____ suddenly
*Virus destroys ___ _____ cells, causing severe ________
*Animals may test ______ for 16 days to 42 days PI, till the animal's immune system produce detectable antibodies.
*Clinical signs include?:
***Chronic form: infections produce ______ tests and classic symptoms: ?
* Inapparent form:
*Healthy animals with no fever or anaemia
*95% of current EIAV population
Symptoms severity =viral load
= transmissibility
7-30, fever, feed, die, red blood, anaemia, negative
*Weight loss *anaemia *oedema
*Stumbles *Unsteady gait * Diphasic fever
positive
-Weight loss, weakness -Anemia
-Swelling of the lower legs, chest and abdomen
-Symptoms subside, but may reoccur
92
How would you diagnose and Control EIAV? EIAV – Diagnosis and control
***Coggins test (AGID): gold standard test for EIAV as per the OIE
recognized for international trade to diagnose EIAV (‘swamp fever’)
*** ELISA: rapid test: can produce false positive
* **Western blot : test for viral proteins not antibodies confirming test may detect the virus before the Abs are formed none quantitative test
*** Q-PCR test:
Can test the presence of the pro-viral DNA in macrophages
Sensitive before eh antibodies formed
Can indicate acute viral load
Can test foal exposure
* Once animal is infected, it becomes a carrier for life
To date there are no satisfactory vaccines for EIAV
The key to prevention is the identification and control of infected horses
An eradication program would be only possible
93
Feline Immunodeficiency Virus (FIV)
Lentivrus
* FIV occurs worldwide, very similar to the virus causes _____ (_____) in humans
* HIV and FIV belong to the same class, _______
* FIV: found mainly in ____ fighting with each other
* FIV : non transmissible to _____ or _____
* FIV : shed in the saliva of infected cats, so the disease spread through bite wounds
* FIV-infected cats may show ______ signs
lethargy, loss of ____, fever, swollen lymph nodes (________), & weight ____
* Signs of FIV infection and ____ infection are very similar
* One serological surveillance for FIV revealed
-In NA: __-___% of cats the tested cats were positive for FIV
-In Latin America about 25% of the tested cats found positive for FIV
* Vaccine is available
AIDS, HIV, Lentiviruses, cats, humans, dogs, nonspecific, appetite, lymphadenopathy, loss, FeLV, 3-5
94
no slide
95
Describe the pathogenesis of FIV
96
CD8+ is a marker because host tries to compromise by MHC-I.
*Emailed Hemida about this*
97
Severe lymphoblastic stomatitis in cat infected with FIV
* Marked _____ and _____ and proliferative lesions in the ______ folds
* Histopathology of a biopsy from a cat with severe _____ due to
FIV infection
hyperemia, ulceration, palatoglossal, stomatitis
98
99
Drop in lymphocytes (lymphopenia)
100
Feline Leukemia virus (FeLV)
Feline Sarcoma virus (FeSV)
1. FeLV belongs to _________
** In US: __-_ % of the cats may be infected with FeLV
** FeSV is a _______ virus derived from ____ that contains an oncogene (__-____) in place of
the ____ gene
* FeLV: associated with both _____ and ____-_____ (immunosuppression) diseases
* FeLV: commonly spread among cats that ____ together
* FeLV: do not survive more than ____ hours outside the cats body unless in ___ environment
Gammaretrovirus, 2-3, defective, FeLV, v-fmsl, env, neoplastic, non-neoplastic, few, wet
101
How is FeLV transmitted?
What is a rare form of transmission?
--> FeLV: transmission:
1. Vertical: from cat to her kitten either in utero or during nursing after birth
2. Horizontal transmission: infected cats (Saliva, tears, urine, mutual grooming)
-Rarely thorough the oral fecal route
-Biting between animals
102
Some serological surveillance found
-In NA: about ___% of the tested cat were positive for FeLV
-In Latin America: up to ___% of the tested cats were positive for FeLV
4, 42
103
* FeLV: usually binds to the ?
* _________ is the most commonly occurring feline tumor associated with FeLV.
T-lymphocytes, Lymphosarcoma
104
What are the Clinical signs of Feline Leukemia virus (FeLV)?
* Loss of appetite, anorexia, weight loss
* Anemia
* Persistent diarrhea
* Poor coat condition
* Conjunctivitis, keratitis, upper
respiratory tract infection
* Behaviors changes
* Neurological disorders
* Abortion in pregnant cats
105
Exogenous FeLV-___ recombines with _______ FeLV sequences to give rise to ?
A, endogenous, the leukemogenic FeLV-B.
106
FeLV-B recombinants use a _____ receptor and have a broader _____. Leukemias caused by _____
mutagenesis
different, tropism, insertional
107
How do you diagnose a cat with FeLV?
Diagnosis of FeLV in cats
* CBC: anemia (lymphopenia, neutropenia, in a response to some secondary infections,
thrombocytopenia, immune mediated hemolytic anemia)
108
Bottom right
109
What is the Prognosis of FeLV infection in cats?
* Diagnosis of FeLV in cats can be ________ devastating
* FeLV infected Cats can live ______ lives for ____ periods of time
* The median survival time for cats after FeLV is diagnosed is ?
* Careful monitoring of ?
- Any signs of abnormality in any of these areas should prompt immediate consultation with a veterinarian.
emotionally, normal, prolonged, 2.5 years, weight, appetite, activity level, elimination habits, appearance of the mouth and eyes, and behavior is an important part of managing FeLV in cats
110
Bioscint Engineering supplies _____ rapid tests for the detection of _____/___ including many other diseases in canines.
Abaxis, FeLV/FIV
111
1. Simian immunodeficiency virus (SIV) of ________ (Pan troglodytes) (SIVcpz) is now well established as the origin of the ? pandemic.
2. Which animals serve as the best models for SIV?
3. Reports of animals in captivity are somewhat ______ and conflicting; some animals also seem to suffer ill effects from SIV infection, whereas others live for _____, ______ developing any clinical signs
1. chimpanzees, human immunodeficiency virus (HIV)-1
2. African green monkeys and sooty mangabeys—
by far the best-described models for SIV
3. anecdotal, decades, without
112
Retrovirus of fish
* A total of ____ proliferative diseases of fish have been associated with the presence of
retroviruses
* Retroviruses have been classified into _____ genera
* Most likely belong to ______: retrovirus genus is associated with _____ in fish
* E.g. ?
13, seven, Epsilonretrovirus, neoplasia, walleye dermal sarcoma virus and snakehead retrovirus
