Feline Immunodeficiency Virus

Also known as: FIV

Description

Feline immunodeficiency virus is a retrovirus that causes immunodeficiency disease in the domestic cat.

Agent

FIV is a member of the genus of the Retroviridae family. For general information about the family see Retroviridae Overview.

FIV was first discovered in a cat rescue facility in the United States where cats had been showing similar clinical signs to people with acquired immunodeficiency syndrome². Subsequently it has been shown that FIV has been present in the cat population since the late 1960s, and that the virus is very similar to the human retrovirus, HIV. However, despite these similarities, FIV is specific to cats, and people cannot become infected with the virus.

Transmission and Epidemiology

The major route of transmission is via saliva, particularly through biting^{2, 3}. Therefore, those cats showing territorial aggression are most at risk of contracting FIV. High levels of virus are found in the saliva of infected cats, particularly those in the stages of acute or terminal infection³. Less commonly, salivary transmission can occur via shared food bowls and mutual grooming. Vertical transmission can occur, either transplacentally or via milk², but venereal transmission has not been reported. The likelihood of infected kittens being born to a FIV-infected mother depends on the stage of infection: up to 70% of kittens are born infected if the queen suffers acute infection during pregnancy, but chronic infection of the mother rarely results in transplacental transmission⁴. The potential role of blood-sucking insects, such as fleas, in spreading infection is unknown².

It is clearly possible that horizontal transmission can occur within multi-cat households, but in some households only a single cat in a group may be FIV positive, whereas in others nearly every cat may be infected. Overall it appears that if fighting among cats housed together is rare, the prevalence of FIV is likely to be low⁴.

FIV infection is prevalent worldwide, with between 1 and 14% of healthy cats and up to 44% of sick cats harboring the virus⁴.

Pathogenesis

The pathogenicity of FIV is strain dependent, and can vary widely. For all strains, feline lymphocytes and macrophages are the preferred cells for virus replication, and so FIV disrupts the function of the immune system. FIV gains entry to the cell via feline CD134, a surface molecule, and uses various chemokine receptors as secondary receptors⁵. In acute infection, the virus spreads from the site of entry to the lymphoid tissues and thymus, where it first infects T-lymphocytes and then macrophages. Although both CD4+ and CD8+ cells can be infected by FIV and lysed in culture, the virus appears to preferentially destroy CD4+ cells. This initially results in a change in the ratio of CD4+ to CD8+ cells, from roughly 2:1 to less than 1:1⁵. After several months of infection, an absolute reduction in CD4+ is appreciable.

Approximately three weeks after infection, cats may show the "primary phase" of FIV infection with malaise, lymphadenopathy and pyrexia². Viraemia peaks at 7-8 weeks and then declines, but increases again in the terminal stages of disease¹. The host then remains asymptomatic for an indefinite period until cell-mediated immunity is disrupted by a decrease in the production of Th1 cytokines. In the advanced stages of infection, humoral immunity is also adversely affected. Although clinical signs are primarily due to changes related to T-cell populations, macrophages are the main reservoir of FIV in infected cats⁵. These cells are capable of transporting virus to various tissues of the body, and also suffer impairment of function, such as an increase in the production of TNF. Microglia and astrocytes in the brain, and megakaryocytes in the bone marrow, can become infected with FIV^{1, 5}, and co-infection with feline leukaemia virus can increase the expression of FIV in many tissues, including the kidneys, liver and brain.

Signalment

Feline immunodeficiency virus occurs frequently in cats throughout the world, and similar viruses have been recovered from wild and zoo felids¹. FIV infection increases in prevalence in older cats, and the average age at diagnosis is 5 years⁵. Male cats are more commonly infected than females as they roam more and exhibit a higher degree of territorial aggression^{2, 3, 4, 5}. There are no breed predilections⁵.

Diagnosis

The signs of feline immunodeficiency virus infection can be very variable, as signs are dependent on the secondary infections that become established. However, differential diagnoses for the immunosuppressive effects and some other primary effects of the virus include feline leukaemia virus infection, toxoplasmosis and the dry form of FIP⁶. Primary bacterial, parasitic, viral or fungal infections should also be ruled out⁵.

Clinical Signs

The clinical signs in the immunosuppressive stage of the disease are related to secondary infections and are therefore extremely variable. Clinically, the associated conditions cannot be distinguished from those occurring in feline leukaemia virus-related immunosuppression. Patients often present with vague signs, such as inappetance or weight loss, and a history of recurrent minor illness related to the gastrointestinal or upper respiratory tract is common. Disease of the oral cavity including gingivitis and stomatitis is frequently seen. This can be linked to secondary pathogens such as calicivirus and oral bacteria. Calicivirus, along with other organisms such as herpesvirus, Toxoplasma gondii and Chlamydia psittaci, can cause ocular signs including conjunctivitis, keratitis, uveitis and chorioretinitis in 35% of cases. Similar microbes give rise to secondary cat flu, and diarrhoea occurs in a quarter of affected cats. Other common signs due to immunosupression include anaemia (due to Haemobartonella felis), meningoencephalitis, pneumonia, glomerulonephritis, renal failure, cystitis and pyoderma, caused by a variety of bacteria. The potentiating effects of FIV on FeLV infection can also induce neoplasia.

The virus itself may also have certain effects. Half of all cats affected display lymphomegaly, and pyrexia occurs in 30% of cases². Anaemia, neutropenia, lymphopenia and thrombocytopenia are commonly seen, as well as diarrhoea and uveitis. Neurological signs, renal disease and neoplasia may also be direct effects of feline immunodeficiency virus.

Laboratory Tests

No typical changes for FIV infection are revealed by routine haematology and biochemsitry. The haemogram may be normal, or anaemia, lymphopenia or neutropenia can be seen, related to the direct effects of the virus. Secondary infection may result in a neutrophilia. Biochemical changes reflect the associated conditions in individual cases⁵.

Diagnosis of FIV is made by demonstrating the presence of antibodies against the virus. ELISA tests are available for in-house use, with some kits detecting antibody to the core protein p24 and others detecting antibody to the envelope protein gp4l². Non-haemolysed plasma or serum is used for performing the in-house ELISA. Results must be interpreted with caution.

Once a cat acquires FIV infection, the antibodies created persist for life. This means that an ELISA test at any stage after infection should give a positive result. However, the test has a sensitivity of 98%, and so false positives do occur. Because of this, animals that test positive to an in-house ELISA, should be re-tested using a different test. Laboratories offer an immunoblot (Western blot) to confirm the diagnosis in cats that are ELISA-positive. The problem of using a test that detects antibodies becomes apparent when it is necessary to test kittens that are born to an FIV-positive queen. Antibodies against FIV are passively acquired via the milk, and can be detected when an ELISA test is used. This makes it impossible to distinguish animals that have been transplacentally infected with virus and are producing their own antibodies from those which have merely acquired pre-formed antibodies from their mother. Maternally derived antibodies can persist for up to 6 months², and so animals testing positive before this age should be retested at 8-12 months old⁵.

Negative results can be true negatives. Alternatively, they may arise when the cat is infected with FIV but the antibodies produced are not detectable by the test used. Conversely, the cat may be infected but antibodies are not present, for example in the first two months of infection². Therefore, if clinical signs give a strong suspicion of FIV infection, or the cat is known to be at risk (for example, recently bitten by and infected cat), animals should be retested 6-8 weeks later and use of an immunoblot should be considered. Up to 15% of cats completely fail to ever mount an antibody response against FIV infection. Virus isolation can be performed but is not widely available outwith the context of research^{4, 5}. An RT-PCR tests is commercially available and detects virus rather than antibody with high specificity, but variations between strains and laboratories may make this test unreliable^{2, 4, 5}.

Pathology

On post-mortem examination, there is lymphadenopathy. Intestinal lesions similar to those seen in feline panleukopenia virus infection may be apparent⁵.

In early disease, lymphadenopathy is seen histologically to be due to follicular hyperplasia and infiltration of plasmacytes to surround the cortex. Later in disease, a mixture of follicular hyperplasia and follicular depletion may exist, and in the terminal stages of FIV infection, follicular involution is the key feature⁵. Lymphoplasmacytic infiltrates are seen in the gingiva, lymphoid tissues, spleen, kidney, liver and brain. Brain lesions also include perivascular cuffing, gliosis, neuronal loss, vacuolation of the white matter and, occasionally, the presence of giant cells.

Treatment

In the sick FIV-positive cat, treatment is aimed at symptomatic and supportive care and management of the secondary infections present. Because these animals are immunosuppressed, their response to antibiotic therapy is often much slower and less successful^{2, 5}. Therefore, much longer courses of antimicrobials are often required in FIV positive cats compared to normal animals. Higher doses may also be necessary^{4, 5}. Antibiotics used should be broad spectrum, with activity against anaerobic bacteria. Combinations including metronidazole or clindamycin are therefore good choices⁵. In inflammatory conditions, such as gingivitis/stomatitis, careful use of anti-inflammatory doses of corticosteroids in combination with antibiosis may be effective in reducing the severity of disease^{2, 4, 5, 6}. Topical steroids may be used in uveitis. Tooth extraction and scale and polishing can also help in the control of gingivitis. Dietary modifications may need to be made, for example in the face of renal disease or diarrhoea⁵, and appetite stimulants such as cyproheptidine can be useful in anorexic cats. Cats should not be fed raw meat and should be discouraged from hunting due to the increased risk of Toxoplasma gondii infection². Griseofulvin is contraindicated in FIV-positive individuals because it can cause a severe neutropenia that can enhance the establishement of secondary infections⁵.

Preventative strategies should also be implemented in the FIV-infected animal in order to protect the cat from acquiring potentially life-threatening infections. This is particularly important as FIV positive animals are often refractory to treatment when secondary infections arise. Ideally, affected cats should be kept indoors to minimise exposure to potential pathogens⁴. Routine vaccination against herpesvirus, calicivirus and panleukopenia and possibly feline leukaemia virus is recommended², and killed vaccines should be favoured as there is a small risk of the attenuated strains in modified live vaccines causing disease in the immunosuppressed patient^{2, 5}. It may also be advisable to administer an extra booster before introducing the cat to a high risk environment, such as a cattery or in hospitalisation if the cat has not received one in the last six months². Treatment against worms and fleas should be kept up to date, particularly to minimise the risk of transmission of Haemobartonella felis.

Some antiviral agents have been shown to give improvement in FIV-infected cats². Zidovudine is the mot effective of these⁵ but can induce bone marrow toxicity and so patients' haematological profile should be closely monitored^{2, 4, 5}. Immunomodulatory products such as feline interferon omega also show some efficacy⁵. Bodyweight, haematocrit and neutrophil count improve with administration of oil of evening primrose², particularly in asymptomatically or mildly affected FIV-positive cats.

Control

As the most significant mode of transmission of FIV is by biting, FIV positive animals should be neutered and, if possible, kept indoors to prevent onward spread of infection. At the very least, infected cats should be kept in at night, since this is when the majority of cat fights occur². In multicat households, the other cats should be tested for FIV antibody. Positive cats can then be segregated or rehomed so that FIV-negative cats do not contract infection. However, if fighting seldom occurs within a household, the risk of horizontal transmission is low and so many owners elect to keep the household as it is. If this is the case, cats should be fed from separate bowls, and bowls, litter trays and other fomites should be routinely disinfected. FIV positive queens should not be used for breeding, and any kittens that do happen to be born from infected mothers should be hand-reared to minimise the risk of infection through milk². Kittens should then be antibody tested after six months of age.

Although an inactivated whole-virus vaccine is available, its efficacy is highly variable and often low after three doses⁵. The vaccine is not available in the UK, and the WSAVA guidelines advise against its use as it can later prevent diagnosis of FIV associated disease by ELISA or immunoblot. One of the major obstacles to vaccine design is the massive genomic variability between FIV strains. It is unlikely that any effective FIV vaccine will appear on the market for several years².

Prognosis

The long-term prognosis for FIV-infected cats is guarded, but some cats will survive for many years following diagnosis. A cat should therefore never be euthanased based on a positive test result for FIV⁴. Around 20% of affected cats die within the first two years after diagnosis; this equates to a 20% mortality rate in the first 4.5-6 years after the estimated time of infection^fmc. In general, the more chronic and severe the clinical signs, the worse the prognosis is. The duration of the asymptomatic period following FIV infection varies with the infecting strain and cannot be predicted. However, cats affected at a younger age are more likely to progress to an immunodeficient state⁴.

Feline Immunodeficiency Virus Learning Resources
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Literature Search Search for recent publications via CAB Abstract (CABI log in required)	Feline Immunodeficiency Virus publications since 2000

Links

• Feline Advisory Bureau FIV Factsheet
• Wikipedia FIV Review

References

1. Wise, D J and Carter, G R (2005) A Concise Review of Veterinary Virology, IVIS.
2. Caney, S (2000) Feline immnunodeficiency virus: an update. In Practice, 22(5), 255-260.
3. Johnson, C M (2005) Transmission of Feline Immunodeficiency Virus. Proceedings of the 56th Annual Meeting of the American College of Veterinary Pathologists and 40th Annual Meeting of the American Society for Veterinary Clinical Pathology.
4. The European Advisory Board on Cat Diseases (2008) Feline Immunodeficiency Virus. Guidelines of Feline infectious Diseases.
5. Tilley, L P and Smith, F W K (2004) The 5-minute Veterinary Consult (Fourth Edition),Blackwell.
6. Rand, J (2006) Problem-based feline medicine, Elsevier Health Sciences.
7. Merck & Co (2008) The Merck Veterinary Manual (Eight Edition), Merial.
8. Morrision, W B (2002) Cancer in dogs and cats: medical and surgical management, Teton NewMedia.

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