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 lentivirus genus of the Retroviridae family. Retrovirus virions are are sensitive to heat, lipid solvents, and detergents but are relatively resistant to damage caused by ultraviolet light¹. The Retroviridae are enveloped viruses which contain a single-stranded RNA genome within an icosahedral nucleocapsid. Glycoprotein surface spikes are located on the envelope. Unusually, Retroviruses have a diplod genome: two identical copies of their positive-sense ssRNA are found on the virion¹. During viral replication, reverse transcriptase converts the ssRNA genome to ssDNA. This process is inherently error-prone, and the high rate of mutation gives rise to a wide genetic diversity of virus¹. A dsDNA can then be made from the ssDNA template. This provirus DNA then becomes integrated into the host genome by the actions of the viral enzyme integrase, and remains latent until transcription is initiated by the host cell machinery¹. Proviral DNA then serves as a template for the production of progeny ssRNA genomes and messenger RNA. Once the proviral DNA has been transcribe and translated, the virions assemble and are release by budding through the host cell membrane. This does not always cause lysis¹.

Many Retrovirus genomes contain oncogenes which may be expressed when integrated to the host genomes. However, oncogenes are not a requirement for tumour induction, and some Retroviruses can cause tumours without carrying oncogenes. The Retroviral genome has four coding regions. The "gag" region codes for the matrix protein, nucleoprotein and capsid, and "pro" encodes a protease¹. Reverse transcriptase is coded by the "pol" region, whereas "env" gives rise to the envelope and receptor binding. An additional, specific cellular transporter RNA is required for replication and present within the virion.

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 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 low.

Since FIV was first isolated in 1986 [Pedersen 1987], serological studies have demonstrated that FIV is endemic in domestic cat populations worldwide; the seroprevalence of FIV is highly variable between regions, with estimates of 1 to 14% in cats with no clinical signs and up to 44% in sick cats [Hartmann 1998]. Sick adult cats, male cats and entire cats are most likely to be infected [Hosie et al. 1989]. The major route of natural transmission is believed to be via the inoculation of saliva during fighting [Yamamoto et al. 1989]. Vertical transmission and transmission between cats in stable households is relatively uncommon. The majority of natural FIV infections are acquired by biting, presumably through the inoculation of virus, or virus-infected cells, from the saliva of persistently infected cats. Transmission from mother to kittens may occur but only a proportion of the offspring become persistently infected. The proportion of kittens infected depends on the viral load of the queen during pregnancy and birth. E.g. if the queen is acutely infected up to 70% of the kittens may be infected, but if the queen is clinically normal but chronically infected hardly any kittens will be infected [O’Neil et al. 1995a, 1995b, 1996]. Although neither oronasal nor venereal spread has been documented in nature, cats can be infected by experimental inoculation of virus into the nose, mouth, vagina and rectum [Moench et al. 1993] and virus can be recovered from semen following natural or ABCD Guidelines on Feline Immunodeficiency Virus 5/21 experimental infection [Jordan et al. 1998]. Queens however may still be infected at mating if bitten by an infected tomcat.

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 receptors^fmc. 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 intially results in a change in the ratio of CD4+ to CD8+ cells, from roughly 2:1 to less than 1:1^fmc. 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 pyrexia. Viraemia peaks at 7-8 weeks and then declines, but increases again in the terminal stages of disease^viro. 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 cats^fmc. 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^{fmc, viro}, 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 felids^viro. FIV infection increases in prevalence in older cats, and the average age at diagnosis is 5 years^fmc. Male cats are more commonly infected than females as they roam more and exhibit a higher degree of territorial aggression. There are no breed predilections.

Diagnosis

Laboratory Tests

• ELISA for serum antibody
  • False positives occur, particularly in the presence of maternal Ab
• Positives can be confirmed by lab work (Western blotting)

Pathology

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

In early disease, lymphadenopathy is seen histologically to be due to follicular hyperplasia and infiltration of plasmacytes to surround the cortex. Later in disese, a mixutre of follicular hyperplasia and follicular depletion may exist, and in the terminal stages of FIV infection, follicular involution is the key feature^fmc. 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.

Prognosis

The long-term prognosis for FIV-infected cats is guarded, but some cats will survive for many years following diagnosis. 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 generally, the more chronic and severe the clinical signs, the worse the prognosis is.

Control

• No UK vaccine
• Healthy positive cats should have diagnose confirmed by further testing
• Isolate and castrate
• Preventative neutering of males

Links

• Feline Advisory Bureau FIV Factsheet

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. Tilley, L P and Smith, F W K (2004) The 5-minute Veterinary Consult (Fourth Edition),Blackwell.
4. 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.
5. Merck & Co (2008) The Merck Veterinary Manual (Eight Edition), Merial.
6. Morrision, W B (2002) Cancer in dogs and cats: medical and surgical management, Teton NewMedia.
7. Rand, J (2006) Problem-based feline medicine, Elsevier Health Sciences.