Lecture 12: Small Ruminant Viruses

Question 1

What is virus induced transformation and how does it happen?

Answer 1

• Transformation: normal cell turning into neoplastic cell
  o Genetic changes in: cell proliferation/differentiation/apoptosis
  o Proto-oncogenes (promote growth), tumor suppressor genes (rregulate protooncogenes)
• Oncogenic viruses: viruses that lead to tumor formation

Question 2

What is the agent causing ovine pulmonary adenocarcinoma

Answer 2

Ovine Pulmonary Adenocarcinoma (OPA)
* Many names: Jaagsiekte
* Agent: Jaagsiekte sheep retrovirus

Question 3

What is the mechanism of ovine pulmonary adenocarcinoma

Answer 3

• Mechanism: epithelial cells in bronchioles and alveoli (type 2 pneumocytes)/lymphocytes/myeloid cells
  o Carry oncogene (E – protein, envelope protein)
• Pathogenesis: go to lung and infect type 2 pneumocytes
  o Infect lymphoid and myeloid cells
  o Virus replicate and express E-protein
   Transform type 2 pneumocytes
  o Tumor growth and metastasis to LN +/- 2 infection
  o Increased fluid production in lung (from tumors) – excrete into environment
  o Large tumors and necrosis and death

Question 4

Where is ovine pulmonary adenocarcinoma located

Answer 4

• Prominent worldwide: NA/Asia/Africa/SA – wherever there are sheep (except Iceland and Australia/NZ)

Question 5

What does ovine pulmonary adenocarcinoma target and what are the clinical signs

Answer 5

• Target: sheep <7-9mo
• Clinically: in sheep >2yo (2-4yo)  fatal after onset of clinical signs
  o In recently infected flocks = higher mortality (30-80%)
  o Flocks infected for a while = lower mortality (1-5%)
  o Dyspnea/ cough – chronic respiratory signs
  o Large amounts of clear frothy fluid
  o Progressive weight loss
  o Wheelbarrow test: lift hind legs and lower head to collect respiratory fluid
   Does not detect all sheep with tumors (must be productive/later stage) = negative doesn’t mean free of disease
  o Carriers are subclinical

Question 6

How is ovine respiratory adenocarcinoma transmitted

Answer 6

• Transmit: respiratory via aerosol/droplet or milk/colostrum
  o Infected animals are lifelong carriers
  o Incubation 3-36mo

Question 7

What are the histologic and gross features of ovine pulmonary adenocarcinoma

Answer 7

• Histo: IHC and IF visualize viral proteins (evidence of viral replication via detecting viral proteins)
  o Antibody detect via ELISA
  o Antigen detect via ELISA
• Gross: frothy trachea and nares
  o Enlarged and edematous lungs (fail to collapse)
  o Focal to diffuse bulky mass
  o Between normal lung architecture and tumor (potentially abscesses in tumors if 2nd infection)
  o Enlarges bronchial and mediastinal LN (10% contain metastasis)

Question 8

How is ovine pulmonary adenocarcinoma diagnosed and treated

Answer 8

• Dx:
  o Clinical: not certain because there can be 2nd infection confounding
  o Lab:– use BAL fluid for RTPCR
   No serology - Ig’s to this virus not detected in serum (b/c no immune response
• Tx: none
  o No immune response because there are endogenous retrovirus elements in thee sheep genome = cannot develop vaccine because it will induce autoimmune rxn
• Prevention: most animals can carry without clinical signs
  o Test + quarantine prior before introducing into flock (but incubation is long time)
  o Single age herd preferable (prevent introducing new infected)
  o Hand raise lambs with milk replacer (because it is transmitted by milk)

Question 9

What is another name for Maedi-Visna and what type of virus is it

Answer 9

Ovine Progressive Pneumonia (OPP)
* Lentivirus – retrovirus

Question 10

How is Maedi-Visna transmitted and what are the clinical signs

Answer 10

• Clinically: most subclinical but some develop fatal disease
  o Dyspnea (Maedi)
  o Neurologic signs (Visna)
  o Reduced milk prod
• Transmit: respiratory/colostrum

Question 11

What are the gross features of Maedi-Visna infections

Answer 11

• Gross: lungs fail to inflate and contain coalescing multifocal gray-white nodules + atelactic nodules in parenchyma
  o Lung – swollen and heavy/not deflated
  o and trachea – thickened mucosa

Question 12

What are the 2 types of Maedi-Visna infection

Answer 12

• Visna form: rare - fatal
  o Brain and spinal cord affected: hindlimb weakness/ataxia/tremor/paresis/paralysis
• Maedi form: respiratory form + mastitis and arthritis + 2 bacterial infections

Question 13

How to diagnose and control Maedi-Visna

Answer 13

• Dx: Agar gel immunodiffusion test/western blot/ RTPCR
• Control: avoid feeding colostrum but virus may have transplacental mechanisms

Question 14

What type of virus is caprine arthritis and encephalitis virus

Answer 14

Caprine Arthritis and Encephalitis
* Lentivirus

Question 15

What animals are affected by caprine arthritis and encephalitis virus and how is it transmitted

Answer 15

• Mainly goats (also sheep)
• Transmit: colostrum and milk

Question 16

What are the 4 clinical/pathological manifestations of caprine arthritis and encephalitis virus

Answer 16

• Clinically: most subclinical – 20% develop into progressive/untreatable dz
  o Poly arthritis – adult
   Swelling around carpus +/- pain and thickening around joints (proliferative and fibrinous synovitis)
   Synovial membrane – edema/hypertrophy/fibrosis/mineralization/necrosis
   Multinucleated syncytia
  o CNS: Encephalomyelitis – kids
   Hind limb paralysis/head pressing
   Invade into white matter
   Lesions: perivascular cuffing/destruction of myelin/discoloured spinal cord and brain/accumulation of mononuclear cells/meningitis
  o Indurative mastitis (hard udder due to lymphocytic infiltration) = reduced milk production
  o Chronic interstitial pneumonia

Question 17

What cell types are targeted by caprine arthritis and encephalitis virus

Answer 17

• Target: macrophage/DC/synovial membrane cells

Question 18

How to diagnose and control caprine arthritis and encephalitis virus

Answer 18

• Dx:
  o Clinically: young (encephalitis + ataxia and inability to adduct hindlimbs)
   If older: arthritis, weight loss, and poor hair coat
  o Path: lymphopenia if chronically infected/marked pleocytosis in CSF/red tinges synovial fluid with high mononuclear cell count
  o Lab: AGID/ELISA
   Also western blot radioimmunoassay/virus isolation/RTPCR/IHC
• Control: no cure/vx
  o Prevent vertical transmission via colostrum and milk
  o If you get 2 negative tests (AGID) 6 months apart = animal negative

Question 19

Another name for orf

Answer 19

Contagious Ecthyma/Orf

Question 20

HHow is orf transmitted, what species does it target, and what type of virus is it

Answer 20

• Target: sheep and goats (also alpaca/muskox/big horned sheep/dogs) – zoonotic
  o High risk for farmers, abattoir workers, vets, shearers
• Poxviridae – parapox virus – orf virus
  o enveloped
• Replicate in epithelial cells (in localized lesions
• Transmit: cut/abrasion – resistant to the enviro because the keratin of the skin protects them

Question 21

incubation period for orf

Answer 21

• Incubation 2-3d

Question 22

What are the clinical signs of orf

Answer 22

• Clinically: resolve in 4 weeks – high morbidity and low mortality
  o Initial papules/pustules/vesicles with inflammation and ulceration – progress to thick brown scabs
• Path: target organ (skin/mucosa) – mouth/nose/eyes/eyelid/feet/udder/perineum

Question 23

What are histo changes of orf

Answer 23

• Histo:
  o Cells (epitheliotropic virus/epidermal keratinocyte)
  o Leading to ballooning degeneration of epithelial cells
  o Replicated in the cytoplasm – intracytoplasmic inclusions (pox virus)

Question 24

How to control orf

Answer 24

• Vaccine: vaccines will induce classical lesions of the disease…
  o Shed virus
  o Vaccine can infect humans
  o Doesn’t produce long lasting immunity

Question 25

What type of virus is blue tongue? What species does it target

Answer 25

Bluetongue
* Reoviridae – obivirus – bluetongue virus
o Many strains (27)
* Target: sheep/cattle/deer/goat/camelid – sheep most severe, cattle – main reservoir

Question 26

How is bluetongue transmitted and where?

Answer 26

• Transmit: Culicoides midges (biting midget) – late summer and fall, can carry virus long distances
• In tropical regions – emerging in CA due to climate change

Question 27

What are the clinical signs of blue tongue

Answer 27

• Clinically (sheep): fever/eye and nasal discharge
  o Drooling (due to ulcers in mouth)
  o Swelling of head and mouth and neck
  o Lameness and inflame at coronary band
  o Difficulty breathing
  o Abortion and developmental abnormalities
  o Serotype 8: Cerebellar aplasia – circling/head pressing/staggering
• Clinically (deer/goat/cattle) – mild, self-limiting

Question 28

Caprine arthritis encephalitis (CAE) is characterised by progressive clinical
syndromes. What is your approach to control this disease? (3 marks).

Answer 28

Answer:
1. No cure and no effective vaccines available,
2. Prevent vertical
transmission through milk and colostrum and

3. Establish a CAEV free farm-
   2 negative AGID tests 6 month apart. Cull the positive animals and keep the negative animals

Question 29

Against Jaagsiekte disease developing a vaccine is not recommended.
Why? (2 marks)

Answer 29

Answer: Approximately 20 copies of enJSRVs integrated in the sheep
genome. enJSRVs are expressed in sheep reproductive tract→ may induce
autoimmune inflammatory reactions when vaccination is attempted
breaking the tolerance.

Question 30

What is TRUE relevant to ovine pulmonary
carcinoma/Jaagsiekte disease

a Is caused by a virus belonging to the Reoviridae family
b Can be transmitted by biting midges
c Wheelbarrow test can be used to detect excess fluid in
lungs in some of the sheep with tumors
d Rising antibody titers determined by paired serum
samples are diagnostic
e Dry trachea and nares are suggestive of the disease

Answer 30

C

Question 31

Two viruses that can be transmitted via feeding colostrum
are
a Bovine corona virus and orf virus
b Bovine respiratory syncytial virus (BSRV) and blue
tongue virus
c Bovine viral diarrhea virus (BVDV) and blue tongue virus
d Bovine leukosis virus and caprine arthritis encephalitis
virus
e Bovine herpes virus 1 and Orf virus

Answer 31

D

Question 32

What is FALSE relevant to clinical manifestation of caprine
arthritis and encephalitis (CAE) virus infection
a Leads to polyarthritis in adults
b Causes polyarthritis in kids
c Encephalomyelitis is common in kids and adults can be
affected
d Leads to indurative mastitis
e Causes chronic interstitial pneumonia

Answer 32

B

Question 33

What is TRUE relevant to orf/ contagious ecthyma
a The causative virus is enveloped and not stable in
the environment
b The causative virus is epitheliotropic
c The vaccines are effective in inducing long lasting
immunity with no side effects
d Primarily affects goats but not sheep
e Due to the narrow host spectrum human infections
are not possible

Answer 33

B