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Virology > Virology of Small Ruminants > Flashcards

Virology of Small Ruminants Flashcards

1
Q

What are the Transmissible spongiform encephalopathies (TSEs) of small ruminants?

A
  • Scrapie - sheep/goats
  • Chronic wasting disease (CWD) - cervids
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2
Q

What is the Etiology of TSE?

A
  • Transmissible Prion - infectious protein particle
    • lacks nucleic acid
  • Normal Host Protein:
    • PrPC = normal protein
      • Membrane bound glycoprotein
      • PRNP gene
      • Alpha helices
      • Expression (though not limited to) Neural and lymphoreticular tissue
  • Altered Protein
    • PrPres = Protease resistant prion protein
      • PrPsc = Scrapie prion protein
      • PrPCWD = Chronic Wasting Disease prion protien
    • Misfolded ⇢ B sheets
    • Highly resistant to UV light, radiation, alcohol, disinfectants (including formalin), and heat
      • Wet heat more effective than dry heat
      • Environmental stability
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3
Q

What are the 9 human prion diseases?

A
  • Kuru (transmissible)
  • 4 forms of CJD (2 transmissible)
  • Gerstmann-Straussler-Scheinker Syndrome
  • 2 forms of fatal insomnia
    • familial
    • spontaneous
  • VPSPR (variably protease-sensitive prionopathy
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4
Q

What are the forms of sheep scrapie?

A
  • Nonclassical or atypical scrapie
    • occurs sporadically in sheep and goats
    • Believed to be nontransmissible (or poorly transmissible) under natural conditions
  • Classical scrapie
    • Transmissible form
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5
Q

Is Scrapie zoonotic?

A

not zoonotic

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6
Q

Is Chronic Wasting disease zoonotic?

A

no solid evidence of transmission to humans

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7
Q

Is Bovine Spongiform encephalopathy prion zoonotic?

A
  • Causative agent of:
    • Variant Creutzfeld-Jakob disease (vCJD) in humans - Zoonotic
    • Feline spongiform encephalopathy in cats
  • Possible origin of transmissible mink encephalopathy
  • Not the same as scrapie or CWD prions
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8
Q

What are the major factors in the pathogenesis of TSE?

A
  • Host PRNP gene and the amino acid sequence of the PrPC protein
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9
Q

What causes the clinical signs of TSE?

A
  • Loss of normal PrPc
  • Accumulation of PrPSc in neurons
  • Cytotoxic effects and vacuolation in the brain (spongiform)
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10
Q

What is the function of PrPC?

A
  • Not fully characterized
    • Normally transported to cell membrane
    • Lysosomal hydrolase degradation (PrPres resistant to this degradation)
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11
Q

What is the pathogenesis of TSE?

A
  1. Transmission
    1. Ingested
    2. Transplacental
  2. Invasion into lymphnode (GALT/RAJ, Retropharyngeal)
    3.
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12
Q

How is TSE transmitted?

A
  • Shed in milk, saliva, feces, and urine
    • Environmental contamination -
  • Prion ingestion
    • Horizontal transmission
      • Placenta, colostrum/milk ingestion, environmental contamination
  • Prenatal transmission
    • Transplacental - vertical transmission
    • Semen ?
    • Embryo transfer (maybe)
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13
Q

What are the clinical signs of scrapie?

A
  • Ataxia - swaying when turning
  • High stepping, tremors
  • Abnormal head carriage
  • Behavioral changes
  • Pruritus (leads to scraping to itch ⇢ “Scrapie”)
  • Chewing or nibbling reaction when back scratched
  • Weight loss, emaciation (not all cases)
  • Always Fatal
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14
Q

How is Scrapie diagnosed?

A
  • Histopathology of Brain (H&E staining) - not definitive
  • Immunohistochemical (IHC) staining - official test
    • Antemortem
      • lymphoid tissue ⇢ Recto-anal junction (RAJ), third eyelid
      • Trained person should collect samples (accredited/trained DVMS, APHIS/State personnel)
    • Post mortem
      • Retropharyngeal lyphnodes, tonsil
      • Braine ⇢ obex
      • Collected by: Producers, accredited DVMs, USDA-APHIS reps, State animal health employees
  • ELISA - confirmatory test (for presence of prion, not antibodies)
  • Western Blot - confirmatory test (for presence of prion, not antibodies)
  • Electron microscopy - detect scrapie associated fibrils (rarely used)
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15
Q

What is the treatment for scrapie?

A

non - Always FATAL

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16
Q

How is scrapie managed?

A
  • Test, monitor, cull
  • National Scrapie Eradication Program
17
Q

How is scrapy prevented?

A
  • Genetic resistance/susceptibility testing
    • Black-faced sheep (Suffolk, Hampshire, Shropshire) and crosses - majority
    • Idetified genetic variants of susceptibility/resistance in sheep
    • Commercially available genetic testing - whole blood, blood card, tissue
    • Goats represent fewer cases
    • Two alleles of susceptibility/resistance also identified in goats
18
Q

How is Scrapie susceptibility inherited?

A
  • Controlled by polymorphisms in codons within PrP gene (PRNP)
  • Sheep:
    • AA at codons 136, 154, 171 affect infectivity PrPC ⇢ PrPSc
      • Codon 171 most important
      • Codon 136 some flocks
      • Codon 154 not important in U.S. Sheep
  • Goats:
    • Codon 146 and 222
19
Q

What are the Alleles for Codon 171?

A
  • Arginine (R), Glutamine (Q)
  • R Confers Resistance ⇢ Dominant genotype
  • Q confers susceptibility
  • Any other amino acid = Q
20
Q

What are the alleles for Codon 136?

A
  • alanine (A), or Valine (V)
  • A confers resistance
  • V confers susceptibility
  • Only important in sheep that are QR at 171
21
Q

What are the important combinations of the 136 and 171 Codons?

A
  • AARR ⇢ Most resistant and do NOT transmit scrapie
  • AAQR ⇢ Less/rarely susceptible to classical scrapie
    • rare cases in Europe
  • AVQR ⇢ less/rarely susceptible to classical scrapie
    • rare cases in US
  • AAQQ, AVQQ, VVQQ ⇢ most susceptible and CAN transmit
22
Q

Can sheep be genotyped for Scrapie’s susceptibility?

A
  • Commercial genetic test approved by USDA APHIS for genotyping sheep
    • 6 USDA approved labs
    • Other labs also offer commercial genotyping
    • Sample ⇢ Whole blood, docked tails
23
Q

What are the important codons within the PRNP gene, and what do they confer?

A
  • Both S146 and K222 appear to be dominant resistance genotypes = fewer goat cases
  • N = Asparagine at position 146 (confers susceptibility)
  • S = Serine at position 146 (confers genetic resistance)
  • Q = Glutamine at position 222 (confers susceptibility)
  • K = Lysine at position 222 (confers genetic resistance)
24
Q

Can goats be genotype tested for Scrapie?

A
  • No commercial genetic test approved by USDA APHIS
  • Genotyping is currently available (UC Davis Veterinary Genetics Laboratory)
    • Sample ⇢ Hair root from coarse, longer hair often found over withers, chest, rmp, tail, back of hind leg, poll, or fetlock is the preferred sample type for goats
25
Q

What is Chronic Wasting Disease?

A
  • TSE of cervids
  • Affects animals 6 months and older
    • most 3-5 years
  • Disease more subtle and prolonged in elk
26
Q

What are the clinical signs of CWD?

A
  • Progressive weight loss
    • Emaciation ⇢ consistent finding
    • Continue to eat, but reduced amounts
  • Difficulty swallowing
    • Hypersalivation
    • Aspiration pneumonia
  • Behavioral changes
    • Listlessness
    • Decreased interaction with herd
    • Depression
    • Lowering head
  • Subtle ataxia, wide based stance
  • Subtle head tremors
  • Excessive drinking and urination
27
Q

How is CWD diagnosed in cervids?

A
  • Histopathology of brain (H&E staining) - not definitive
  • Immunohistochemical (IHC) staining - most common
    • Antemortem - no currently approved methods
    • Postmortem:
      • Retropharyngeal lymph nodes, tonsil
      • Brain - Obex
  • ELISA - USDA approved method (presence of prion, not antibodies
28
Q

What are the ancillary diagnostics for TSE testing for?

A
  • Use antibodies that recognize PrPres
  • No immune response to prions ⇢ No available serology test
29
Q

How is CWD transmitted?

A
  • Horizontal - Blood, saliva, urine, and feces infective
  • In utero
  • Environmentally stable
    • Contaminated pens/pastures infective for years
    • Attempts at disinfection so far futile
30
Q

How is CWD controlled on commercial Game Farms?

A
  • Double fencing - keep from spreading to and from wildlife
  • Buy only from free herds
  • Depopulate or quarantine infected herds
  • Do not restock contaminated premises
  • Prevent access of wild cervids to contaminated areas
  • USDA Program - test all animals that die for 5 years
    • USDA APHIS National CWD Voluntary Herd Certification Program - herds must participate to move interstate
31
Q

Does genotype matter for transmission of CWD?

A
  • Research shows regardless of genotype, animals are able to shed infectious prions in saliva, urine, and feces throughout most of the disease course

Virology (37 decks)

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