Feline leukemia virus in Cats (Felis) | Vetlexicon
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Feline leukemia virus

ISSN 2398-2950

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Synonym(s): Feline leukaemia virus, FeLV

Introduction

Classification

Taxonomy

  • Family: Retroviridae.
  • Group: Gammaretrovirus.
  • Subtypes A ,B, C, and T determined by host cell spectrum.

Etymology

  • Retro because the viral RNA is reverse transcribed into DNA (proviral DNA).

Distribution

  • Worldwide.
  • 0.5-1% prevalence in healthy cats in the UK.
  • Higher prevalence in sick cats.
  • In multicat households with endemic FeLV, 30-40% will develop persistent viremia.

Significance

  • 3 disease syndromes:
    • Immunosuppression.
    • Proliferative (neoplasia, leukemia).
    • Degenerative (anemia, leukopenia).
  • In cat:
    • Immunosuppressive.
    • Oncogenic, causing T-cell lymphosarcomas Lymphoma.
    • Reproductive failure: abortion, failure to conceive.
    • Anemia Anemia: overview.
    • Enteritis.
  • In human:
    • Not zoonotic (Nowotny et al, 1995).
  • Other species:
    • Does not infect non-felidae.

Active Forms

Active Form 1

Morphology

  • Enveloped, single stranded RNA virus. Diploid.
  • Surrounding the nucleic acid is an icosahedral capsid, known as the core. The core protein, p27, is detected in many FeLV-diagnostic tests FeLV test.
  • Contains the enzyme reverse transcriptase, that reverse transcribes the viral RNA genome into DNA, which becomes integrated into the host cell genome (proviral DNA).

Tolerances

Temperature
  • Survives in plasma up to 4 days at room temperature. Poor survival outside host if not protected by blood components, a matter of minutes only, therefore survival on, for example, food dishes is negligible.
  • Remains infectious if kept moist at room temperature, hence iatrogenic transmission may occur via contaminated needles, surgical instruments or blood transfusions.

Development

Reproduction
Viral replication
  • Once the virus has bound to the cell the envelope fuses with the plasma membrane liberating the viral core into the host cell cytoplasm.
  • The RNA genome of the virus is then reverse transcribed into DNA by the reverse transcriptase enzyme.
  • This DNA copy (provirus) migrates to the nucleus where it becomes integrated into cellular chromosomal DNA.
  • The provirus may remain transcriptionally silent within the cell in latent infection (up to 50% of cats which have survived exposure to FeLV remain latently infected in the bone marrow for months to years afterwards, the infection being contained by the immune system).
  • However, in non-immune cats or immunosuppressed latently infected cats, once the cell starts to divide, full length transcripts form new FeLV RNA, viral proteins are produced and the viruses bud from the surface of the infected cell.
Longevity
  • 85% of FeLV-infected cats are dead within 3.5 years of diagnosis.

Resting Forms

Clinical Effects

Epidemiology

Lifecycle

  • Lymphoid tissue in oropharynx   →   low titer viremia   →   systemic lymphoid tissue   →   bone marrow   →   high titer viremia   →   salivary gland and intestinal epithelia.
  • Following ingestion, the virus grows in the cells of the oropharynx and is transported via mononuclear cells in the blood to the bone marrow.
  • FeLV grows in the bone marrow, releasing p27 and virus into the plasma.
  • Virus reaches other organs and multiplies in the tissues where there are dividing cells, such as the epithelial cells of the oropharynx, upper respiratory tract and salivary glands.
  • The incubation period between infection and viremia is from 2-3 weeks onwards.
  • If cat doesn't clear the infection before virus reaches bone marrow, the cat is more likely to become persistently infected.

Transmission

  • Large amounts of virus is shed in the saliva, virus may also be shed in the urine and milk.
  • The virus is fragile, therefore transmission occurs directly from cat to cat.
  • Requires long periods of close contact to infect adult cats as older cats  become increasingly able to mount an effective immune response after 4 months of age.
  • Transplacental transmission also occurs - kittens often diein uteroor are stillborn.
  • FeLV transmission to kittens has been recorded in a latently infected non-viremic cat via the milk (Pacitti et al, 1986).

Pathological effects

  • Cats that overcome viremia usually have high titers of virus neutralizing antibodies (VNA). Cell-mediated immunity is important; not all immune cats develop VNA and protected vaccinated cats do not have demonstrable VNAs.
  • Immunosuppression - main cause of death.
  • Thymic lymphosarcoma Lymphoma: mainly young cats (under 3 years old).
  • Multicentric lymphosarcoma Lymphoma.
  • Alimentary lymphosarcoma Lymphoma.
  • Lymphoid leukemia Chronic lymphoid leukemia.
  • Myeloid leukemia Myeloid leukemia.
  • Anemia: mainly non-regenerative Anemia: overview.
  • Reproductive disorders are observed rarely nowadays  Infectious infertility in the female.

Control

Control via chemotherapies

  • Interferon-omega Interferon reduces the number of healthy FeLV-infected cats showing clinical signs and increases longevity.
  • The antiretroviral compound 3'azido-2',3'-dideoxythymidine (AZT) can reduce viral load and increase longevity. Side-effects (non-regenerative anemia) may develop at high doses.
  • If FeLV-infected cats are sick, prompt and accurate diagnosis is important for early treatment with appropriate medication.
  • Immunosuppressive drugs including corticosteroids should be avoided unless used to treat FeLV-associated malignancies or immune-mediated disease.
  • Blood transfusions Blood transfusion may be useful in anemic cats.
  • Granulocyte colony-stimulating factor can be considered in leukopenic cats.
  • Treatments for lymphosarcoma Lymphoma using vincristine Vincristine, prednisolone   Prednisolone  and cyclophosphamide Cyclophosphamidehave been described (Squires & Gorman, 1990).
  • Some cases of lymphoma respond well to chemotherapy, leading to remission in many cases and some cats showing no recurrence within 2 years.

Control via environment

  • FeLV is easily killed by any disinfectant.
  • FeLV-positive cat can remain healthy with good quality of life for months or years. It is important to isolate from other cats to protect both the FeLV-infected cat as well as the uninfected contacts.

Vaccination

  • Vaccination is recommended for all cats at risk of exposure from 8-9 weeks of age and again at 12 weeks, with a booster 1 year later to complete the primary vaccination course.
  • ABCD does not recommend reliance on vaccination to protect FeLV-negative cats living together with FeLV-infected cats.
  • Most vaccine manufacturers recommend annual boosters.
  • ABCD suggests booster vaccination at 2-3 year intervals is sufficient for cats over 3-4 years of age as adults are significantly less susceptible to FeLV infection.
  • There are several FeLV vaccines available: the first was an inactivated virus vaccine but newer vaccines contain either the viral envelope protein expressed inE.colior a canarypox virus carrying genes encoding viral proteins.

Other countermeasures

  • A highly effective strategy for the prevention of FeLV infection is by testing and prevention of uninfected cats contacting infected cats. This system has been successfully used to maintain the FeLV-free status of most serious cat breeders.
  • All the cats in the household are FeLV tested and FeLV-negative cats are separated from FeLV positive cats.
  • The cats are retested after 12 weeks, at which time any cats incubating FeLV should test positive and any which were only transiently positive should test negative.
  • Again, positive and negative cats are separated.
  • Any new cats entering the FeLV-free household should test FeLV negative before admission.
  • Annual retests are strongly advised.

Diagnosis

Useful samples

Virus isolation

  • Virus isolation usually produces a positive result first, followed within a few days by DNA and RNA PCR PCR (Polymerase chain reaction), ELISA Enzyme linked immunosorbent assay (ELISA), and then later by immunofluorescence (IFA) Indirect immunofluorescence.
  • Virus isolation can be performed by Companion Animal Diagnostics at the University of Glasgow; virus may be isolated from plasma or bone marrow using cell culture techniques and can take 1-2 weeks.
  • DNA PCR and IFA can be performed by specialized laboratories (the University of Bristol, Langford and Companion Animal Diagnostics at the University of Glasgow respectively in the UK).
  • The test to determine whether a cat is protected from FeLV infection measures virus neutralizing antibodies. This test can be conducted by Companion Animal Diagnostics at the University of Glasgow.

Sampling

  • ELISA Enzyme linked immunosorbent assay (ELISA) for p27 antigen is the most common screening test in diagnostic laboratories.
  • 1 ml serum, plasma, whole blood in heparin for virus isolation or p27 ELISA.
  • Whole blood smears may be prepared for IFA although few laboratories now offer this test as an option.
  • Bone marrow in specialized transport medium for detection of latent infection.
  • 1 ml serum, plasma or whole blood in heparin for virus neutralizing antibody testing.

Specimen storage

  • Samples not immediately to be posted should be separated (ie plasma or serum removed) and stored at -20°C.

Transport of samples

  • First class post is usually sufficient provided reaches laboratory within 24-48 hours.
  • Inadvisable to send samples before bank holiday.

Isolation

  • Antibody testing not done routinely in US - ELISA most common.
  • Detection of virus neutralizing antibodies (VNA) is useful in a household of cats where one cat has been diagnosed and confirmed as being FeLV positive.
  • The question arises whether it is best to separate the FeLV positive cats from the FeLV negative cats.
  • The FeLV negative cats can be tested for VNA: cats with antibody titers of 16 or higher are immune and it is safe to leave them in contact with the FeLV positive cat(s). (Not done routinely in the US).
  • Cats with VNA titers of less than 16 should be separated from the FeLV positive cat(s). (Not done routinely in the US).
    Note that vaccination does not induce VNA, therefore this test cannot be used to establish whether vaccinated cats are protected from FeLV infection.

Field diagnosis

  • FeLV should be suspected in any cat which seems immunosuppressed, eg which has recurrent pyrexia, recurrent upper respiratory tract problems Rhinitis, abscesses that won't heal. Any cat presenting with a tumor or anemia Anemia: overview should also be FeLV tested.
  • Several tests are available for detecting the FeLV protein p27 in the veterinary surgery. Immunomigration tests include SNAP FeLV, IDEXX Laboratories Inc., USA; Duo Speed FeLV/FIV, Bio Veto Test, France; Witness, Synbiotics, USA. It is vital to realize that these tests may give either false positive or false negative results and that positive tests in a healthy cat or negative results in a FeLV-like sick cat should always be confirmed by virus isolation or PCR.

Laboratory diagnosis

  • ELISA test Enzyme linked immunosorbent assay (ELISA) on saliva/tears not good as a screening test as it does not detect early stages of infection.
  • Samples are screened for p27 in the veterinary laboratory usually using a plate ELISA. In house ELISA kits are also available. Retest healthy positive cat in 1 month to see if virus was cleared.
  • Immunomigration tests may also be used in the laboratory setting, for example SNAP FeLV, IDEXX Laboratories Inc., USA; Duo Speed FeLV/FIV, Bio Veto Test, France; Witness, Synbiotics, USA.
  • Virus isolation can be performed by specialized laboratories.
  • Virus isolation is the gold standard in FeLV diangosis, the test takes about 1-2 weeks. The virus is grown in cell culture of specially-adapted indicator cell lines. (Not performed routinely in US.) 
  • At least 80% of cats with thymic lymphosarcomas are FeLV positive.
  • 60% of cats with multicentric lymphosarcomas are FeLV positive.
  • Only 30% of cats with alimentary lymphosarcomas are FeLV positive (this tumor more commonly occurs in an older age group of cat and some are caused by FIV).
  • FeLV immunofluorescence is still offered by some laboratories although its use is being largely superseded by molecular techniques such as real-time PCR.

Discordant cats

  • These are cats which have p27 in their blood, but no virus can be grown in cell culture.
  • Most have probably been transiently infected and are becoming immune, however, such cats may remain positive by DNA PCR (ie are latently infected) and some do eventually become viremic, so it is advisable to monitor these cats as chronic stress, immune suppression or co-infection with other viruses may lead to viral reactivation..
  • Discordant cats should be considered as potential sources of infection.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Lutz H, Addie A, Belák S et al (2009) Feline leukaemia. ABCD guidelines on prevention and management. J Feline Med Surg 11 (7), 565-574 PubMed.
  • Muirden A (2002) Prevalence of feline leukaemia virus and antibodies to feline immunodeficiency virus and feline coronavirus in stray cats sent to an RSPCA hospital. Vet Rec 150 (20), 621-625 PubMed.
  • Dawson S, Gaskell R & Jarrett O S (1999) Vaccination in cats - an update. In Practice 21 (2), 71-74 VetMedResource.
  • Nowotny N, Uthman A, Haas O A et al (1995) Is it possible to catch leukaemia from a cat? The Lancet 346 (8969), 252-253 PubMed.
  • Squires R & Gorman N T (1990) Antineoplastic chemotherapy in cats. In Practice 12 (3), 101-111 VetMedResource.
  • Pacitti A M, Jarrett O, Hay D (1986) Transmission of feline leukaemia virus in the milk of a non-viraemic cat. Vet Rec 118 (14), 381-384 PubMed.

Other sources of information

  • Jarrett O (1994) Feline leukaemia virus. In: Feline Medicine and Therapeutics. Chandler E A, Gaskell C J, Gaskell R M (eds). Blackwell Science, Oxford, OX2 OEL. pp 473-487.
  • McCaw D L (1994) Advances in therapy for retroviral infections. In: Consultations in Feline Internal Medicine. August J R (ed). pp 21-25.

Organization(s)

  • Companion Animal Diagnostics,Veterinary Diangostic Services, Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Glasgow, G61 1QH, Scotland. Tel: + 44 141 330 5777; Fax: + 44 141 330 5748; E-mail:  companion@vet.gla.ac.uk .
  • Department of Veterinary Medicine, Bristol University, Langford House, Langford, Bristol, BS18 7DU.
  • European Advisory Board on Cat diseases (ABCD): www.abcd-vets.org .