Feline retroviruses

What are the feline retroviruses

• Feline leukaemia (FeLV) - type c mammalian retrovirus

• Feline immunodeficiency virus (FIV) - lentivirus

• Feline synctium forming virus (FeSFV) - spumavirus

• Endogenous viruses

What is virus classification based on

• The geonome

• Number and sense of RNA and DNA strands

• Morphology

• Genome sequence similarity

• Ecology

What are the key properties of Retroviridae

Enveloped ssRNA viruses with genone organisation 5’-gag-pro-pol-env-3’

What does the gag gene encode

Internal structure proteins matrix, capsid and nucleocapsid produced by proteolytic processing

What does the pro gene encode

Viral protesases which cleaves gag, pro, pol and env products

What doe the pol gene encode

Reverse transcriptase which contains DNA polymerase and integrase for geonome replication

What does the env gene encode

Surface glycoprotein and transmembrane protein forming the receptor binding complex

How does retroviridae replicate

What are two unique features of Retroviridae replication

• Their genome is made by host transcription machinery with no viral polymerase involved

• Their positive sense RNA cannot act directly as mRNA after infection

What is the role of Reverse Transcriptase in Retroviridae

A viral RNA-dependent DNA polymerase that synthesises complementary DNA from the viral RNA genome

What is the role of Integrase in Retroviridae

Binds viral cDNA and host DNA to inset the viral genome into the host genome

What are endogenous retroviruses

Remnants if ancient retroviral insertions into germ cells that now make up 8% of human DNA

How are endogenous retroviruses transmitted

Vertically as permanent parts of the host genome

What diseases are endogenous retroviruses associated with

• Various cancers

• Autoimmune diseases

• Neurological disorders

What biological roles do endogenous retroviruses play

• Placentation

• Early embryogenesis

• Foetal development

What are the three subtypes of feline leukaemia virus

A, B and C distinguished by genome analysis and serology

What type of FeLV subtype is transmissable and most common

Type A

How do FeLV types B and C arise

As recombinants between type A and endoenous retroviruses or as mutants of type A

How is FeLV excreted

• Saliva

• Urine

• Faeces

• Milk

What type of contact is usually required for FeLV transmission

Close friendly contact

Does FeLV transmit vetically

yes vertical and transplacental transmission are common

What does PCR detect in PeLV diagnosis

Decects PeLV proviral DNA integrated into host cells

What does RT-PCR detect is FeLV diagnosis

Detects FeLV viral RNA in blood or tissues

What does a lateral flow test detect in FeLV diagnosis

Detects FeLV antigen circulating in blood

Where does FeLV first replicate after ingestion

Oropharynx and local lymph nodes

What follows primary viraemia in FeLV infection

Replication in other lymphoid tissues and bone marrow

What occurs after secondary viraemia in FeLV infection

1. Persistent viraemia

2. Clinical disease

3. Death or virus elimination

What are the possible outcomes of FeLV infection aside from persistent viraemia

Virus elimination or persistent latent infection with rare viraemia and shedding

What do test results show in primary viraemia

• Provirus positive in PCR

• Antigen positive

• Antibody negative

• Virus positive in RT-PCR

What do test results show in persistent latent infection

• Provirus positive

• Antigen negative

• Virus negative in blood

• Antibody positive

What do test results show in persistent viraemia

• Provirus positive in PCR

• Antigen positive

• Antibody postive

• Virus positive in RT-PCR

What are the main sources of FeLV virus exposure

Contact with persistently infected cats and in utero transmission

How does age affect FeLV susceptibility

• It decreases with age

• Only 1 in 5 cats over 16 weeks become persistently infected

What immune factors are protective against FeLV

• VN antibody

• Maternal derived antibody protects for 4 weeks

What disease syndromes can FeLV cause

• Reproductive failure

• Anaemia

• Immunodeficiency

• Neoplasia

How does FeLV A contribute to neoplasia

By sporadic insertion near cellular oncogenes activating proto-oncogenes or distributing tumour suppressor genes

What can common FeLV integration sites be used for

Studying oncogenesis

What are the four main types of FeLV-associated lymphoma

• Mediastimal

• Multicentric

• Alimentary

• Leukaemic

Besides major lymphoma types where else can FeLV neoplasia occur

• Kidney

• Nose

• Eye

• Skin

• CNS

What are the clinical signs of alimentary lymphoma

• ANorexia

• Weight loss

• Anaemic

How do you diagnose alimentary lymphoma

• Radiography

• Biopsy

What are the clinical signs of mediastinal lymphoma

• Tachypnoea

• Dyspnoea

• Regurgitation

• Weight loss

What is seen of a clinical exam on medialstinal lymphoma

• Muffled heart sounds

• Palpate increased thoracic resistance

How is mediastinal lymphoma diagnosed

• Ultrasound

• Radiography

• Biopsy

What are the clinical signs of multicentric lymphoma

• Posterior paralysis

• Renal failure

What can be seen on a clinical exam of multicentric lymphoma

Peripheral gross lymphadenopathy

How is multicentric lymphoma diagnosed

• Clinical signs

• Biopsy

What are the clinical signs of leukaemia

• Pyrexia

• Weakness

• Anorexia

What can be seen on a clinical exam of leukaemia

Haemorrhage

How is leukaemia diagnosed

• Haemotology

• Biopsy of bone marrow

What characterises primary FeLV anaemia

• Red cell aplasia

• Total marrow aplasia

• Non-regenerative

• Normocytic

• Normochromic

What FeLV subtype is associated with primary anaemia

Subtype C as mutation allows infection of erythroid precursors

What characterises secondary FeLV anaemia

• Regenerative anaemia due to myeloid tumours in bone barrow

• Haemolytic anaemia is common but often milk and missed

What is the term for FeLV-associated immunosuppression

FAIDs

What clinical problems are associated with FAIDS

• Secondary infections

• Poor wound healing

• Abscessation

• Chronic respiratory or enteric infections

What are common clinical signs in FAIDS-affected cats

• Thin

• Persistently ill

• Pyrexia

• Gingivitis

• Increased risk of haemobartonella

• FIP

• Panleukopnea-like enteritis

When does fetal resorption typically occur in FeLV-infected queens

At 3-5 weeks of pregnancy

What happens to kittens that survive to birth from FeLV-infected queens

They are persistently infected and may develop fading kitten syndrome

What is the purpose of a test-and-remove (T&R) programme for FeLV

To rehome or euthanise persistently viraemic cats essential in colonies

How is vaccination used in FeLV control

As part of colony management alongside T&R

What simple management measure helps reduce FeLV transmission

One food bowl per cat

What is the first step in a FeLV test-and-remove programme for colonies?

Test all cats with a lateral flow test and house all positives seperately

What cats can join the main colony after the 12-week retest

Cats that are negative twice or cats positive once then negative

What should be done with cats that were negative first and positive at the 12-week retest?

House separately and retest again in 12 weeks

What is the outcome for cats testing positive twice

They should be permanently removed from the colony

How often should all colony cats be retested

Every 6-12 months with all new entries being tested

What types of FeLV vaccines are available

• Killed

• Subunit

• Recombinant canarypox

When is the FeLV vaccine given

First at 8-9 weeks old then a booster 3 weeks later

Are FeLV vaccines considered core

They are considered non-core but annual boosters are optional

What is the main approach to treating FeLV

Largely supportive care

Are there specific antivirals for FeLV

No drugs effective in cell culture are often toxic to cats

What treatment may prolong survival in FeLV cats

Interferon

Can lymphomas in FeLV cats be treated

Some can with cytotoxic drugs but other problems usually develop

What is feline immunodeficiency virus

A lentivirus related to HIV

What does FIV cause

Immunodeficiency and associated with a variety of lesions

Is FIV zoonotic

No it is not

What is the prevalence of FIV

Less then 5% in doemstic cats world wide

Which cats is FIV more common in

• Males

• Free roaming

• Feral

• Unstable colonies

How is FIV transmitted

• Biting

• Transplacental

• Milk

What does FIV infect

CD4 T-cell lymphocytes

How does FIV gradually develop

1. Decreases CD4

2. Decreases mitogen and antigen proliferation assays

3. Decreased expression of MHC II

Where is FIV isolated from

• Blood

• CSF

• Lymphoid organs

• Saliva

How is FIV treated

Mainly supportive

How is FIV prevented and controlled

• Prevent cats fighting

• Keep indoors

• Isolate infected cats

What vaccinations are there for FIV

• Non in Europe

• Fel-O-Vax FIV used on USA, Oz and NZ

• Whole inactivated virus

What is the structure of rotraviruses

How is FIV and FeLV diagnosed

• In house latent flow tests

• IF

• IFAT

• Isolation

• Western blot

• PCR

• RT-PCR

What types of in-house lateral flow tests (LFT) are used for FeLV/FIV diagnosis

• SNAP - Idexx

• DUO speed - biovet test

• FASTest - Megacor

• WITNESS - Synbiotics

• One step - EVL

Why is FeLV testing based on antigen rather than antibody

• Most seropositive cats have cleared viraemia

• Vaccination can affect results

• Antibody levels can fluctuate

Why is FIV testing based on antibody rather than antigen

• Virus isolation is slow and expensive

• Early virus levels fluctuate

• No vaccine interferes

• Antibodies remain high

• Cats cannot clear infection

What happens in FeLV tests

1. Biological sample containing p27 antigen binds to antibody 1

2. Aqueous environment of membrane leads to migration of particles

3. p27 acts as a bridge to immobilise the particles by binding to antibody 1 and 2

4. Results in positive test

What do postive immunoflorescence FeLV tests look like

What happens in FIV tests

1. Biological sample containing FIV antibodies binds to FIV antigen in sample well

2. Aqueous environment of membrane leads to migration of particles

3. FIV antibody in test sample acts as a bridge to immobilise the particles by binding to both FIV antigens

4. Results in FIV positive test

What does an immunoflorescence antibody test in FIV look like

What happens in Western blot test for FIV

1. Viral proteins separated by gen electrophoresis

2. Transferred to membrane

3. Patient antibodies bind to specific FIV proteins

4. Detection confirms infection

What gives a false positive when measuring FIV antibodies

Maternally derived antibodies when younger then 6 months

What gives a false negative when measuring FIV antibodies

• Seroconversion at less than 12 weeks

• Decrease in serum antibody

What causes false positives in lateral flow tests

Cat anti-mouse antibody

What is sensitivity

Proportion of true positives picked up by the test

What is specificity

Proportion of true negatives picked up by the test