Family: Rhabdoviridae Flashcards

1
Q

Where does Rhabdoviridae get its name?

A

Rhabdos = rod
- bullet-shaped virion

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2
Q

In North America, which species are most commonly affected by Rabies virus? Infection almost worldwide, what are some exceptions?

A
  • skunks
  • foxes
  • raccoons
  • bats
  • dogs
  • cats

Hawaii, Japan, Great Britain, and some other smaller islands

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3
Q

What was Lagos bat virus initially isolated from?

A

fruit bats - Lyssavirus

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4
Q

What is the structure of Rhabdoviridae virions like? What is its genome like? Where does it replicate?

A

bullet-shaped, enveloped with large spikes, and a helically coiled cylindrical nucleocapsid

negative-sense ssRNA molecule

cytoplasm

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5
Q

How do vesiculoviruses and street rabies viruses compare in their effect on host cells?

A

VSV = rapid cytopathology
SRV = non-cytopathogenic

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6
Q

What 5 subgenomic proteins are translated by Rhabdoviridae RNA-dependant RNA polymerase?

A
  1. L = RdRP
  2. G = glycoprotein
  3. NP = nucleoprotein
  4. P = phosphoprotein
  5. M = matrix protein
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7
Q

Distinguishing characteristics of the four families of Mononegavirales:

A
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8
Q

What 3 genera make up Rhabdoviridae?

A
  1. Ephemerovirus
  2. Lyssavirus
  3. Vesiculovirus
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9
Q

Rhabdoviridae classification:

A
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10
Q

Rhabdoviridae replication:

A

exit = budding

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11
Q

What the reservoir of Rabies virus? How is it transmitted? What are the major and minor sources of the virus?

A

wild animals

wild animal and unvaccinated dog/cat vectors

MAJOR = saliva from the bite of a rabid animal
MINOR = aerosols in bat caves containing rabid bats

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12
Q

What 3 groups of people are at risk for transmitting Rabies virus?

A
  1. veterinarians and animal handlers
  2. people bitten by rabid animals
  3. inhabitants of countries with no pet vaccination program
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13
Q

What 2 epidemiological cycles of Rabies virus transmission are recognized?

A
  1. CANINE (URBAN) = stray dogs accounting for 95% of human cases in developing countries
  2. SYLVANTIC = wildlife species varying geographically, including foxes, coyotes, raccoons, skunks, jackals, mongooses, bats
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14
Q

What is characteristic of Rabies virus infection?

A

lymphoid perivascular cuffing and intracytoplasmic inclusion Negri bodies found most consistently in the pyramidal cells of the hippocampus

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15
Q

What are the 6 steps of Rabies virus pathogenesis?

A
  1. raccoon/vector is bitten by a rabid animal
  2. rabies virus enters through saliva
  3. rabies virus spreads through the nerves and to the spinal cord/brain (gray matter)
  4. virus incubates in the body for 3-12 weeks with no signs of illness or possibility to spread
  5. virus reaches the brain and multiplies rapidly, then reaches the salivary glands and signs of disease begins to show and virus can spread
  6. infected animal usually dies within 7 days of becoming sick
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16
Q

How does inoculated Rabies virus move in the host?

A

in nerve tissue, NOT BLOOD

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17
Q

What animals are affected by Rabies virus? Which are not? How is it mostly transmitted?

A

warm-blooded animals with fur (+humans!)

birds, snakes, fish

in the saliva from a bite of a rabid animal

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18
Q

How does Rabies virus affect host cells? What happens at the site of the bite?

A

not very cytolytic - remains cell-associated

virus replicates in the muscle with minimal or no symptoms and binds to nicotinic acetylcholine receptors on postsynaptic membranes at the NMJ

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19
Q

What 4 things affect the incubation period of Rabies virus?

A
  1. infectious dose
  2. proximity of infection to the site of the CNS and brain
  3. strain of the virus
  4. host immunity
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20
Q

How does the incubation period of Rabies virus compare in animals and humans?

A

ANIMALS = few weeks to a few years, but typically 1-3 months

HUMANS = usually 3-8 weeks; rarely 9 days or 7 months

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21
Q

What are the 2 types of Rabies viruses?

A
  1. street virus - virus recovered from naturally occurring cases of Rabies in the saliva of infected animals
  2. fixed virus - virus with a short, fixed, and reproducible incubation period prepared by repeated culture in the brain of rabbits
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22
Q

How does Rabies virus move once it reaches nervous tissue?

A

retrograde axonal transport with CNS dissemination and centrifugal spread along sensory and autonomic nerves

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23
Q

What is the difference between retrograde and anterograde movement along nerves?

A

RETROGRADE = spreads from axon terminals to the neuronal cell body (opposite of nerve impulse)

ANTEROGRADE = spreads from neuron cell body to the axon terminals (with nerve impulse)

24
Q

What are the 2 forms of Rabies based on clinical presentation?

A
  1. FURIOUS - animal becomes restless, nervous, aggressive, and dangerous and loses fear of humans
  2. DUMB/PARALYTIC - dysfunction, inability to swallow water due to pharyngeal paralysis giving rise to hydrophobia, excessive salivation, exaggerated response to light and sound, hyperesthesia, encephalitis gives way to paralysis
25
Q

What are the terminal signs of Rabies virus infection?

A

convulsive seizures, coma, and respiratory arrest
- death occurs 2-14 days after onset of clinical signs

26
Q

What are 8 common clinical signs that point towards Rabies infection?

A
  1. general sickness
  2. problems swallowing
  3. abundant drool or saliva
  4. animal bites anything (pica)
  5. animal appears tamer than expected
  6. animal has trouble moving or is paralyzed
  7. bat on the ground
  8. rough coat, eye exudate, contracted pupils, protrusion of nictitating membranes
27
Q

What are the 2 phases of human infection with Rabies virus?

A
  1. prodrome phase - weeks to months after inoculation, virus infects peripheral nerves and travels up the CNs to the brain; lasts for 2-10 days
  2. neurologic phase - infection of the brain causes classic symptoms, coma, and death
28
Q

What are 8 clinical signs of Rabies virus infection in humans?

A
  1. disorientation/hallucinations
  2. paralysis
  3. episodes of terror and excitement
  4. hydrophobia
  5. hyperventilation
  6. hypersalivation
  7. seizures, coma, death
  8. (rarely) Guillan-Barre syndrome, a fatal autoimmune disease
29
Q

What 4 areas of the brain are suitable for Rabies virus testing? Can samples be frozen?

A
  1. midbrain
  2. pons and medulla
  3. brainstem
  4. hippocampal neurons

NO - brain tissue is fragile, freezing can interrupt viral nucleic acids and proteins

30
Q

How should large animal, bat, and small animal sampled be submitted to the lab for Rabies testing?

A

LARGE ANIMALS: head only
BATS: whole animal, do not crush head
SMALL ANIMALS: whole animal

31
Q

By the time neurological symptoms occur in humans and animal infected by Rabies virus, ….

A

it is too late —> diagnosis must be done postmortem

32
Q

What are the 2 best indications for diagnosing Rabies virus infection? What else can be done?

A
  1. presence of aggregates of viral nucleocapsids (Negri bodies) in Purkinje cells within the hippocampus
  2. presence of perivascular cuffing or inflammation around a blood vessel in the brain
  • detection of Rabies antigens, antibodies, RNA
  • viral isolation
  • direct immunofluorescence
  • ELISA
  • IHC of antigens in neurons
33
Q

Rabies virus inclusion bodies and perivascular cuffing:

A
34
Q

What should be done if an animal is bit by another rabid animal?

A
  • quarantine for 10 days
  • if animal becomes ill: euthanize and submit for testing (chill, not frozen)
35
Q

Clinical rabies is….

A

almost always fatal unless treated with a post-exposure prophylaxis and a rabies titer (estimation of an immune response against Rabies virus)
- possible due to long incubation period and production of resulting antibodies can block the progression of the virus

36
Q

What is the Rabies pre-exposure vaccination? Why is it given?

A

series of 3 rabies vaccines to be considered pre-exposure to Rabies in case those most likely to come into contact with rabid animals are bitten (veterinarians, animal handlers, lab workers)

eliminated the need for Rabies immune globulin (RIG), which is ONLY given to those who have never received a vaccination (can interfere with response to boosters)

37
Q

What is the Rabies pre-exposure vaccination schedule?

A

three 1.0-mL injections of either a human diploid cell-based (Imovax) or a purified chick embryo-based (RabAvert) administered IM in the deltoid
- days 0, 7, and 21/28

38
Q

What is the indicator of Rabies virus replication? What are the 2 guidelines for titers requiring booster doses?

A

rapid fluorescent focus inhibition test (RFFIT)

  1. Advisory Committee on Immunuization Practices - titer less than 1:5 dilution br RFFIT should receive a booster
  2. WHO: titers above 0.5 IU/mL are adequate for Rabies protection - anthing below requires a booster
39
Q

What are the 3 inactivated whole virus vaccines available for humans against Rabies virus?

A
  1. nervous tissue preparations: rare complication of demyelinating allergic encephalitis
  2. duck embryo vaccine: lower risk for allergic encephalitis
  3. human diploid cell vaccine (HDCV): best available with efficacy rate of ~100% with rare severe reactions (very expensive

(other cell cultures are being developed for developing nations due to the expense of HDCV)

40
Q

How are inactivated (killed) viral vaccines for Rabies given? What is a common example?

A

SQ administered into the abdominal wall

Vaccinia poxvirus rabies vaccine - introduces G protein from rabies into the vaccinia virus and is used as an oral bait vaccine administered to wild carnivores from aircrafts

41
Q

How is vesicular stomatitis virus (VSV) transmitted to animals and humans?

A

ANIMALS: sandfly and blackfly vectors causing seasonal outbreaks; direct contact with other infected animals and contaminated objects

HUMANS: direct contact with infected tissues, vesicular fluid, and saliva; blackfly and sandfly bites; aerosols in the lab

42
Q

Vesicular stomatitis virus (VSV) transmission:

A
43
Q

What is the pathogenesis of vesicular stomatitis virus (VSV)?

A
  • transmitted mechanically by arthropods (sandflies, mosquitoes, blackflies, midges, houseflies)
  • virus enters body through breaks in the skin and mucosa
  • virus can be transmitted through fomites (food, milking machines, restraint devices)
  • VSV then causes local vesiculation, epithelial denudation, and interstitial edema without systemic viremic phases
44
Q

How does vesicular stomatitis virus (VSV) spread after it has already infected a host?

A

extension of the lesion such that the entire epithelium of the tongue or teats can slough off

45
Q

What is the first sign of vesicular stomatitis virus (VSV) infection in pigs? Cattle and horses? What are the most common following symptoms in each?

A

PIGS: lameness; vesicular lesions in snout and coronary band; oral, mammary gland, coronary band, and interdigital lesions

CATTLE: fever and excessive salivation; anorexia, lameness, and rejection of suckling calf; oral, mammary gland, coronary band, and interdigital lesions

HORSES: fever and excessive salivation, chomping, mouth rubbing; severely affected with tongue and coronary band lesions with sloughing, lameness

46
Q

What is the morbidity and mortality rates of vesicular stomatitis virus like?

A

MORBIDITY: 5-90%, most animals seroconvert

MORTALITY: higher in adults, death is rare in cattle and horses

47
Q

What are the 4 vesicle-forming viruses differential diagnoses?

A
  1. foot and mouth disease
  2. vesicular stomatitis
  3. swine vesicular disease
  4. vesicular exanthema of swine
48
Q

What should be done before any samples are taken for suspected vesicular stomatitis cases? How can it be diagnosed in the lab?

A

notify the proper authorities and ensure samples are sent under secure conditions and only to authorized labs to prevent spread

  • virus isolation
  • viral antigen detection from vesicular fluid or epithelium with ELISA, complement fixation, or virus neutralization
  • antibody tests: paired serum samples, ELISA, complement fixation, virus neutralization
49
Q

What are the 7 clinical signs of vesicular stomatitis virus infection in humans? Why is diagnosis difficult?

A

INFLUENZA-LIKE SYMPTOMS
1. headache
2. fever
3. retrobulbar pain
4. malaise
5. nausea
6. limb and back pain
7. oral vesicles (rare)

flu-like illness, so many do not seek treatment, serology needed
- Ddx: Coxsackie A group virus, hand, foot, and mouth disease, herpes simplex

50
Q

What does bovine ephemeral fever virus (BEFV) cause?

A

three-day sickness —> bovine (cattle, water buffalos) epizootic fever of Japan

  • clinical signs persist for 3 days and disappear suddenly with complete recovery
  • noncontagious
51
Q

What is characteristic of bovine ephemeral fever virus (BEFV) infection?

A

sudden onset of fever, depression, stiffness, lameness, and rapid recovery

52
Q

What is the incubation period of bovine ephemeral fever virus (BEFV)? What 2 things influence this? What age of bovine are most susceptible?

A

2-4 days —> rarely 9 days

  1. strain
  2. dose

6-24 months

53
Q

What animals are not known to be infected with bovine ephemeral fever virus (BEFV)? How is it transmitted? Why is it theorized to not be spread by the consumption of infected meat?

A

sheep, goats, other animals

in nature, only by bite of Culicoid mosquitoes
- cannot spread cow-to-cow, by close contact, droplet infection, or body secretions

virus is rapidly inactivated at pH levels below 5, which is attained rapidly in bovine muscle after death

54
Q

What are 7 clinical signs of bovine ephemeral fever virus (BEFV)?

A
  1. morbidity 30%, low mortality
  2. biphasic or triphasic
  3. discharge from the eyes and nose
  4. muscle tremors
  5. temporary lameness
  6. lying down with hindlimbs outstretches to relive muscle cramps
  7. coma and death
55
Q

What are the 2 genera of Rhabdoviruses affecting fish?

A
  1. Novirrhabdovirus - infectious hematopoietic necrosis virus, viral hemorrhagic septicemia virus, Hirame rhabdovirus, snakehead rhabdovirus
  2. Vesiculovirus - spring viremia of carp virus, ulcerative disease rhabdovirus, pike fry rhabdovirus