Viral diseases of lymphoid system Flashcards
What are the main mechanisms by which feline leukaemia virus causes disease?
Immunosuppression, neoplasia, anaemia
What are the main mechanisms by which feline immunodeficiency virus (FIV) causes disease?
Immunosuppression, neoplasia, anaemia
What are the main mechanisms by which equine infectious anaemia causes disease?
Immunecomplexes
What are the main mechanisms by which infectious bursal disease virus causes disease?
Immunosuppression
What are the main mechanisms by which aleutian disease virus causes disease?
Immune complexes
What are the main mechanisms by which malignant catarrhal fever causes disease?
Hyperimmune disease
Give examples of apharetoviruses that cause immune disease
- Avian luekosis
- Rous sarcoma
What genus does Jaagsiekte sheep retrovirus belong to?
Betaretrovirus
What genus does feline leukaemia virus belong to?
Gammaretrovirus
What genus does bovine leukaemia virus belong to?
Deltaretrovirus
What genus do fish tumour viruses belong to?
Epsilonretroviruses
List lentiviruses that affect the immune system
- Human immunodeficiency virus
- Feline immunodeficiency virus
- Equine infectious anaemia virus
- Caprine arthritis-encephalitis virus
- Maedi-Visna virus
Identify the notifiable retroviruses that affect the immune system
- Bovine leukaemia virus
- Equine infectious anaemia virus
Outline how cats can become persistently infected with feline leukaemia virus
- Most will clear virus and recover, some do not
- PI cats are usually younger and mount less robust immune response, realistically die within 1-2 years
- More at risk if born to unvaccinated dams
Describe the clinical signs of feline leukaemia virus
- Leukaemia
- Lymphoma
- Anaemia
- Immunosuppression
- Enteritis
Explain the viral migration of feline leukaemia virus
- Oronasal infection
- Infects lymphocytes in oropharynx, then to local LNs-
- Virus infects local LNs, travels to bone marrow and other lymphoid tissues, then to mucosal tissues
- Incubation period 3-6 weeks until virus found in blood and excreted in saliva
In a cat infected with FeLV, the Ag, viral culture and PCR are all negative. What stage is the cat at regarding the viral migration and describe this stage
- Has invaded local lymphoid tissue, but not invaded bone marrow yet
- Inapparent, local infection
- “Abortive infection”
In a cat infected with FeLV, the Ag is -ve, viral culture -ve and PCR +ve. What stage is the cat at regarding the viral migration and describe this stage
- Has invaded the bone marrow but not the mucosal tissue yet
- May be hard to find on PCR
- Latent infection aka “regressive infection”
In a cat infected with FeLV, the Ag is +ve (may also be -ve), viral culture -ve and PCR+ve (may also be -ve). What stage is the cat at regarding the viral migration and describe this stage
- Has left bone marrow and invaded mucosal tissue, leading to focal infection
- Transient viraemia, “regressive infection”
In a cat infected with FeLV, the Ag, viral culture and PCR are all positive. What stage is the cat at regarding the viral migration and describe this stage
- Virus is shed
- Persistent viraemia, progressive infection
- Do not develop a proper antibody response
Explain the pathogenesis of equine infectious anaemia virus
- Immune complex formation
- Complement activation leads to anaemia, thrombocytopaenia, pyrexia
- Episodic pyrexia/illness associated with emergence of viral variants
Explain the pathogenesis of Aleutian disease of mink
- Parvo
- Viral antibody complexes formed but not eliminated
- Leads to immune complex disease
List the viral infection associated with disorders of haematopoiesis
- Feline leukaemia virus
- Lentiviruses (FIV, EIA, BIV)
Outline the prevalence of FeLV
- Variable
- Decreased due to vaccination and test/removal schemes
Explain the pathogenesis of FeLV
Immunosuppression probably due to virus replication in cell progenitors in BM
What are the different subtypes of FeLV and how are these classified?
A, B, C and T, classified based on viral envelope protein sequence
Describe FeLV A
Isolated in all infected animals
Describe FeLV B (development and consequences)
- Arises due to homologous recombination between A envelope and endogenous FeLV related DNA
- Increases rate of tumour formation
Describe FeLV C (development and consequences)
- Arises, rarely, de novo due to point mutations in the envelope
- Causes severe rapid fatal aplastic anaemia
- All blood cells fall in the animal affected
Describe FeLV T
- Targets T lymphocytes
- Causes severe immunosuppression
Describe the transmission of FeLV
- Close contact required (labile in environment)
- Transmitted by milk, saliva of dam, transplacental infection
- Transplacental usually die in uterua
- Response to infection determines PI or not
Outline the diagnosis of FeLV
- Aim to identify persistently viraemic cats
- NO antibody to virus so detect antigen
- Can use in house ELISA
- Confirm positive results wih virus isolation or immunofluorescence
- qPCR
Discuss the interpretation of the ELISA of FeLV
- Negative results reliable, NPV >99% (but still consider clinical signs and retest if no other cause found after 12 weeks)
- Positive results may be false (PPV 70-90%)
- All positive results should be tested by virus isolation or immunofluorescence
What may cause false positives when testing for FeLV?
- Blood haemolysis
- Incorrect test use-
- Antigen cross reaction
How is FeLV definitively confirmed?
- qPCR
- Detects provirus in circulating WBCs, not viraemia
- NPV very high, but need to consider viral load
Outline the control and management of FeLV
- Correct diagnosis of PI cats
- Test and removal
- Symptomatic and supportive treatment
- Impact on chemotherapy of cancers
- Vaccination of at risk cats
Explain how Lentiviruses evade the host immune responses
- Virus accessory genes
- Decrease MHC expression so less lymphocyte recognition of infected cells
Describe the pathogenesis of Lentiviruses
- Persist via cycles of cell killing, viral release and re-infection (waves of disease - high viral load early, then drops as immune response mounted, then rises once immune response depleted)
- Cell destruction leads to disease
- Infect macrophages/monocytes +/- lymphocytes
- No chance of recovery following infection
Describe the immunopathogenesis of FIV
- Infection of CD4 Th lymphocytes
- Decreased CD4 cell count
- Marked lymphadenopathy
- Virus also targets CD8 T cells, B cells, macrophages and glial cells
- Lymphoid tissues of intestine may also be affected
- Follicular destruction/dysplaisa seen in later stages of disease
Describe the signs of FIV
- Acute transient illness severel weeks after exposure
- Long asymptomatic carrier state
- Chronic disease with secondary infections e.g. respiratory, oronasal, enteric, urinary
- Severe disease in terminal stages: anaemia, cachexia, diarrhoea, leukopaenia, opportubistic infections
- Uveitis, gingivitis, CNS infection
Describe the formation of tumours in FIV
- Rare compared to FeLV
- B cell lymphomas
- Extranodal: gut, liver, spleen
Which cats are more at risk of FIV?
Older male entire strays/free ranging cats
Describe the transmission of FIV
- Horizontal, mainly by biting
- Rarely transplacental, may be associated with biting through umbilicus
- Kittens born to infected dams receive MDAs which persist until 16 weeks of age
Describe the prognosis for FIV
Longer than FeLV
Describe the diagnosis of FIV
- Detection of antiviral Ab using snap test/ELISA
- Cats may be Ab negative up to 12 weeks post infection
- Young kittens born to FIV + dams will have maternally derive antibody, wait or test with PCR based test
Describe the control of FIV
- Control feral cat population
- Prevent transmission from known FIV positive cats (reduce fighting e.g. no new cats in household, but may entire through gum abrasions, allogrooming)
- Vaccination not available in UK
Outline the treatment of FIV
- Palliative
- Dental care, antibiotics etc.
Describe the transmission of equine infectious anaemia
Transmitted by biting insects e.g. horseflies
Describe the clinical signs in the acute phase of equine infectious anaemia infection
- Fever, diarrhoea, lethargy, restlessness, colic, rapid breathing, naal and ocular discharge, emaciation, oedema, paralysis of hindquarters
- Anaemia
- High levels circulating virus
Describe the diagnosis of equine infectious anaemia virus
- Confirm negative by Coggins test - agar gel immunodiffusion test detects antibody
- Test plasma of all imported horses
Outline the treatment and control of EIA
- NO vaccines
- Poor treatment options
Describe infectious bursal disease virus
- Highly resistant and contagious
- Affects 2-6 week old chicks
- Tropism for lymphocytes in bursa and thymus
Describe the clinical signs of infectious bursal disease
- Watery diarrhoea
- Cloacal inflammation
- Secondary infection
- Oedematous bursa
Describe the histopathological appearance of a bursa affected by infectious bursal disease virus
- Loss of lymphocytes leads to loss of purple rings of follicles
- Cysts in chronic infection
Explain the pathogenesis of infectious bursal disease
- Tropism for lymphocytes
- Viral protein VP2 induces apoptosis of lymphocytes
Outline the treatment of infectious bursal disease
No treatment
Outline he control of infectious bursa disease
- Emergency of very virulent (VV) strains makes control difficult
- Difficult to eliminate
- Attenuated or recombinant vaccines used with variable efficacy
- Controlled by vaccination of breeding stock adngood biosecurity
Describe the pathology and signs of Aleutian mink disease
- Glomerulonephritis
- Splenomegaly
- Areritis
- Ferrets: ascending paralysis
Describe the clinical findings in malignant catarrhal fever
- Single animals
- Depressed, anorexic, mild drop, weight loss
- Nasal and ocular discharges
- Corneal oedema
- Marked pyrexia (>41°C), sweating
- Oral, nasal ulceration
- Lymphadenopathy
Outline the diagnosis of malignant catarrhal fever
- Clinical signs highly suggestive
- Confirm by antiviral (OHV-2) Ab detection or PCR
Outline the management of malignant catarrhal fever
- No effective treatment
- No vaccine
- Avoid mixing sheep/cattle around lambing time
- Management systems in zoo collections (Wildebeest are reservoirs)
Outline the transmission of malignant catarrhal fever
- Sheep (and Wildebeest) are natural hosts, not affected
- Cattle are dead end hosts
Outline the effect of feline infectious peritonitis on the immune system
Immune complex formation
Outline the effect of bovine viral diarrhoea on the immune system
Immunosuppression predisposes to respiratory disease complex in calf or calf diarrhoea
Outline the effect of parvovirus on the immune system
- Panleukopaenia: decrease white blood cell count
- Killing of lymphoid and myeloid stem cells
Describe a logical testing protocol for a shelter to test for FeLV and FIV
- Isolate/quarantine when arrive (although can carry FeLV and FIV for life so not useful for these diseases specifically)
- Selective testing of at risk cats: stray, entire,
- FIV positive cats: advise indoor lifestyle
- FeLV positive on second test: do not rehome, poor prognosis
