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. 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 virion^viro. During viral replication, reverse transcriptase converts the ssRNA genome to ssDNA. A dsDNA can then be made from the ssDNA template. This provirus DNA then becomes integrated into the host genome, where it serves as a template for the production of progeny ssRNA genomes and messenger RNA. The host cell's transcription mechanisms perform these tasks.

   * The conversion of ssRNA to ssDNA, mediated by the viral enzyme reverse transcriptase, results in a dsDNA molecule longer than that of the original genome. This dsDNA migrates to the nucleus where it is ultimately integrated into the host chromosome by the viral enzyme integrase.
   * Once integrated into the host genome, the viral dsDNA is referred to as a provirus. The provirus remains latent until "triggered" into transcription of mRNA by host cell machinery.
   * Viral mRNA transcription of the provirus is mediated by cellular RNA polymerase II.
   * The new virions are released by budding, which does not always result in cell lysis.
   * There is a high mutation rate, as reverse transcription is an error-prone process. Thus, retroviruses usually present a high genetic diversity.
   * Many retroviruses carry oncogenes (e.g., Rous sarcoma virus in chickens), while others do not (e.g., human T-cell lymphotrophic virus). However, some retroviruses may cause tumors without carrying oncogenes.
   * All retroviral genomes consist of two molecules of ssRNA, (+)sense, have 5' cap and 3' poly-(A) (equivalent to mRNA) and four characteristic coding regions (gag-pro-pol-env). Gag (group specific antigen: matrix protein, nucleoprotein, capsid) genes; pro (protease) gene; pol (reverse transcriptase and RNase-H); and env (envelope, receptor binding) genes (see Fig.15.2). These vary in size from ~8-11 kb. They are the only viruses that are truly diploid. Additionally, there is a specific type of cellular transporter RNA (tRNA) (usually trp, pro or lys) - required for replication that is present in the virion.
   * The virions are sensitive to heat, lipid solvents, and detergents but are relatively resistant to ultraviolet light damage.

Transmission and Epidemiology

The major route of transmission is via saliva, especially through biting, and those cats exhibiting territorial aggression are most at risk of infection. Vertical transmission can also occur but the importance of this is not known. Venereal transmission has not been reported. Within households horizontal transmission can occur but the level of infection can be very variable. 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.

Seroepidemiological surverys of the prevalence of FIV in the UK have shown that 13-19% of sick cats may be infected with FIV compared to 2-3% of healthy cats.

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. Tilley, L P and Smith, F W K (2004) The 5-minute Veterinary Consult (Fourth Edition),Blackwell.
3. Caney, S (2000) Feline immnunodeficiency virus: an update. In Practice, 22(5), 255-260.
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.