Feline immunodeficiency virus

Feline immunodeficiency virus
Virus classification
Group: Group VI (ssRNA-RT)
Order: Unassigned
Family: Retroviridae
Subfamily: Orthoretrovirinae
Genus: Lentivirus
Species: Feline immunodeficiency virus

Feline immunodeficiency virus (FIV) is a lentivirus that affects cats worldwide. From 2.5% up to 4.4%[1][2] of cats worldwide are infected with FIV. FIV differs taxonomically from two other feline retroviruses, feline leukemia virus (FeLV) and feline foamy virus (FFV), and is more closely related to human immunodeficiency virus (HIV). Within FIV, five subtypes have been identified based on nucleotide sequence differences coding for the viral envelope (env) or polymerase (pol). FIV is the only non-primate lentivirus to cause an AIDS-like syndrome, but FIV is not typically fatal for cats, as they can live relatively healthily as carriers and transmitters of the disease for many years. A vaccine is available although its efficacy remains uncertain. Cats will test positive for FIV antibodies after vaccination.[3]

FIV was first isolated in 1986 by Dr. Smith at the UC Davis School of Veterinary Medicine in a colony of cats that had a high prevalence of opportunistic infections and degenerative conditions and was originally called Feline T-lymphotropic Virus (FTLV).[4] It has since been identified as an endemic disease in domestic cat populations worldwide.[5]

Effects

FIV can attack the immune system of cats, much like the human immunodeficiency virus (HIV) can attack the immune system of human beings. FIV infects many cell types in its host, including CD4+ and CD8+ T lymphocytes, B lymphocytes, and macrophages. FIV can be tolerated well by cats, but can eventually lead to debilitation of the immune system in its feline hosts by the infection and exhaustion of T-helper (CD4+) cells.

FIV and HIV are both lentiviruses. However, humans cannot be infected by FIV, nor can cats be infected by HIV. FIV is transmitted primarily through saliva (bites), such as those incurred during territorial battles between males. Cats housed exclusively indoors are much less likely to be infected, provided they do not come in contact with infected cats.

A vigilant pet owner who treats secondary infections can assist an infected cat to live a reasonably long life. The chance that an FIV infected cat will pass the disease on to other cats within a household remains, and increases with serious fighting or biting.[6] There is a quantifiable risk that cats living outside of a home can spread the disease to others and can also spread the disease in a group setting in a shelter. Cats living alone as a single pet, rarely left to roam free, pose a diminished but existent risk.

FIV infects other feline species, and in fact is endemic in some large wild cats, such as African lions.

In the United States

Consensus in the United States on whether there is a need to euthanize FIV infected cats has not been established. The American Associations of Feline Practitioners (an organization in the United States), as well as many feral cat organizations, recommend against euthanizing FIV-positive cats, or even spending funds to test for the virus, as spaying or neutering cats seems to effectively control transmission (spayed / neutered cats are less likely to engage in territorial fights).

Pathology

The virus gains entry to the host's cells through the interaction of the envelope glycoproteins (from the glycoprotein env) of the virus and the target cells' surface receptors. First the SU glycoprotein binds to CD134, a receptor on the host cell. This initial binding changes the shape of the SU protein to one that facilitates interaction between SU and the chemokine receptor CXCR4. This interaction causes the viral and cellular membranes to fuse, allowing the transfer of the viral RNA into the cytoplasm where it is reverse transcribed and integrated into the cellular genome through non-homologous recombination. Once integrated into the host cell's genome, the virus can lay dormant in the asymptotic stage for extended periods of time without being detected by the immune system or can cause lysis of the cell. (4,5) [7][8]

CD134 is predominately found on activated T cells and binds to OX40 ligand causing T-cell stimulation, proliferation, activation, and apoptosis (3). This leads to a significant drop in cells which have critical roles in the immune system. Low levels of CD4+ and other affected immune system cells cause the cat to be susceptible to opportunistic diseases once the disease progresses to feline acquired immune deficiency syndrome (FAIDS).[9]

Transmission

The primary modes of FIV transmission are deep bite wounds and scratches, where the infected cat's blood-tainted saliva enters the other cat's bloodstream. FIV may also be transmitted from pregnant females to their offspring in utero, however this vertical transmission is considered to be relatively rare based on the small number of FIV-infected kittens and adolescents .[3][9] This differs from FeLV, which may be spread by more casual, non-aggressive contact since the virus is also present at mucosal surfaces such as those in the mouth, rectum, and vagina, so casual contact cannot be ruled out as a potential transmission.

Risk factors for infection are being of the male sex, adulthood, and outdoor access. One case study conducted in São Paulo found that 75% of the FIV-infected cats were males. Higher rates of infection in males than females makes sense because the primary means of transmission is from biting and most instances of biting in cats occur in fights over territory, an activity more common for males than females.[8]

Disease stages

FIV progresses through similar stages to HIV in humans. The initial stage, or acute phase, is accompanied by mild symptoms such as lethargy, anorexia, fever, and lymphadenopathy.[9] This initial stage is fairly short and is followed by the asymptomatic stage. Here the cat demonstrates no noticeable symptoms for a variable length of time. Some cats stay in this latent stage for only a few months, but for some it can last for years. Factors that influence the length of the asymptomatic stage include the pathogenicity of the infecting virus and FIV subtype (A-E), the age of the cat, and exposure to other pathogens. Finally the cat progresses into the final stage known as the feline acquired immune deficiency syndrome (FAIDS) stage where the cat is extremely susceptible to secondary diseases which inevitably are the cause of death.[8]

Testing

Veterinarians will check a cat's history, look for clinical signs, and possibly administer a blood test for FIV antibodies. FIV affects 2-3% of cats in the US and testing is readily available. It should be noted that this testing identifies those cats that carry the FIV antibody, and does not detect the actual virus.

False positives occur when the cat carries the antibody (which is harmless), but does not carry the actual virus. The most frequent occurrence of this is when kittens are tested after ingesting the antibodies from mother's milk, and when testing cats that have been previously vaccinated for FIV. For this reason, neither kittens under 8 weeks nor cats that have been previously vaccinated are tested.

Kittens and young cats that test positive for the FIV antibody may test negative at a later time due to seroreversion, provided they have never been infected with FIV and have never been immunized with the FIV vaccine.

Cats that have been vaccinated will test positive for the FIV antibody for the rest of their life due to seroconversion, even though they are not infected. Therefore, testing of strays or adopted cats is inconclusive, since it is impossible to know whether or not they have been vaccinated in the past. For these reasons, a positive FIV antibody test by itself should never be used as a criterion for euthanasia.[10]

Tests can be performed in a vet's office with results in minutes, allowing for quick consultation. Early detection helps maintain the cat's health and prevents spreading infection to other cats. With proper care, infected cats can live long and healthy lives.

Treatment options

In 2006, the United States Department of Agriculture issued a conditional license for a new treatment aid termed Lymphocyte T-Cell Immunomodulator (LTCI).[11] Lymphocyte T-Cell Immunomodulator is manufactured and distributed exclusively by T-Cyte Therapeutics, Inc.[12]

Lymphocyte T-Cell Immunomodulator is intended as an aid in the treatment of cats infected with feline leukemia virus (FeLV) and/or feline immunodeficiency virus (FIV), and the associated symptoms of lymphocytopenia, opportunistic infection, anemia, granulocytopenia, or thrombocytopenia. The absence of any observed adverse events in several animal species suggests that the product has a very low toxicity profile.

Lymphocyte T-Cell Immunomodulator is a potent regulator of CD-4 lymphocyte production and function.[13] It has been shown to increase lymphocyte numbers and Interleukin 2 production in animals.[14]

Lymphocyte T-Cell Immunomodulator is a single chain polypeptide. It is a strongly cationic glycoprotein, and is purified with cation exchange resin. Purification of protein from bovine-derived stromal cell supernatants produces a substantially homogeneous factor, free of extraneous materials. The bovine protein is homologous with other mammalian species and is a homogeneous 50 kDa glycoprotein with an isoelectric point of 6.5. The protein is prepared in a lyophilized 1 microgram dose. Reconstitution in sterile diluent produces a solution for subcutaneous injection.

Vaccine

As with HIV, the development of an effective vaccine against FIV is difficult because of the high number and variations of the virus strains. "Single strain" vaccines, i.e. vaccines that only protect against a single virus variant, have already demonstrated a good efficacy against homologous FIV strains. A dual-subtype vaccine for FIV released in 2002 called Fel-O-Vax (ATCvet code: QI06AA10 (WHO)) made it possible to immunize cats against more FIV strains. It was developed using inactivated isolates of two of the five FIV subtypes (or clades): A Petaluma and D Shizuoka.[15] The vaccine was shown to be moderately protective (82% of cats were protected) against subtype A FIV,[16] but a later study showed it to offer no protection against subtype A.[17] It has shown 100% effectiveness against two different subtype B FIV strains.[18][19] Vaccination will cause cats to have positive results on FIV tests, making diagnosis more difficult. For these reasons the vaccine is considered "non-core", and the decision to vaccinate should be made after discussion with a veterinarian and consideration of the risks vs. the effectiveness.[20]

Structure

Genome structure of FIV based on available data 2013.

FIV displays a similar structure to the primate and ungulate lentiviruses. The virion has a diameter from 80 to 100 nanometers and is pleomorphic. The viral envelope also has surface projections that are small, 8 nm, and evenly cover the surface.[7]

The FIV virus genome is diploid. It consists of two identical single-strands of RNA in each case about 9400 nucleotides existing in plus-strand orientation. It has the typical genomic structure of retroviruses, including the gag, pol, and env genes. The Gag polyprotein is cleaved into matrix (MA), capsid (CA) and nucleocapsid (NC) proteins. Cleavage between CA and NC releases a nine amino acid peptide, while cleavage at the C-terminus of NC releases a 2kDa fragment (p2). The Pol polyprotein is translated by ribosomal frame-shifting, a feature shared with HIV. Cleavage of Pol by the viral protease releases the protease itself (PR), reverse transcriptase (RT), deoxyuridine triphosphatase (dUTPase or DU) and integrase (IN). The Env polyprotein consists of a leader peptide (L), surface (SU) and transmembrane (TM) glycoproteins. In common with other lentiviruses, the FIV genome encodes additional short open reading frames (ORFs) encoding the Vif and Rev proteins. An additional short ORF termed orfA (also known as orf2) precedes the env gene. The function of OrfA in viral replication is unclear, however the orfA-encoded product may display many of the attributes of HIV-1 accessory gene products such as Vpr, Vpu or Nef.

The capsid protein derived from the polyprotein Gag is assembled into a viral core (the protein shell of a virus) and the matrix protein also derived from Gag forms a shell immediately inside of the lipid bilayer. The Env polyprotein encodes the surface glycoprotein (SU) and transmembrane glycoprotein (TM). Both SU and TM glycoproteins are heavily glycosylated, a characteristic that scientists believe may mask the B-cell epitopes of the Env glycoprotein giving the virus resistance to the virus neutralizing antibodies.[7]

Lentiviral vector

Like HIV-1, FIV has been engineered into a viral vector for gene therapy.[21] Like other lentiviral vectors, FIV vectors integrate into the chromosome of the host cell, where it can generate long-term stable transgene expression. Furthermore, the vectors can be used on dividing and non-dividing cells.[21][22] FIV vectors could potentially be used to treat neurological disorders like Parkinson's disease, and have already been used for transfer RNAi which may find use as gene therapy for cancer.[23]

See also

References

  1. ↑ Valéria Maria Lara, Sueli Akemi Taniwaki, João Pessoa Araújo Júnior (2008), "Occurrence of feline immunodeficiency virus infection in cats", Ciência Rural 38 (8): 2245, doi:10.1590/S0103-84782008000800024.
  2. ↑ Richards, J (2005), "Feline immunodeficiency virus vaccine: Implications for diagnostic testing and disease management", Biologicals 33 (4): 215–7, doi:10.1016/j.biologicals.2005.08.004, PMID 16257536.
  3. 1 2 American Association of Feline Practitioners (2002), "Feline Immunodeficiency Virus", Cornell Feline Health Center (Cornell University, College of Veterinary Medicine), retrieved 2008-11-12
  4. ↑ Pedersen NC; Ho EW; Brown ML; et al. (1987), "Isolation of a T-lymphotropic virus from domestic cats with an immunodeficiency-like syndrome", Science 235 (4790): 790–793, doi:10.1126/science.3643650, PMID 3643650.
  5. ↑ Zislin, A (2005), "Feline immunodeficiency virus vaccine: A rational paradigm for clinical decision-making", Biologicals 33 (4): 219–20, doi:10.1016/j.biologicals.2005.08.012, PMID 16257537.
  6. ↑ (American Association of Feline Practitioners 2002)
  7. 1 2 3 Lecollinet, Sylvie; Jennifer Richardson (12 July 2007), "Vaccination against the feline immunodeficiency virus: The road not taken", Comparative Immunology Microbiology & Infectious Disease 31: 167–190, doi:10.1016/j.cimid.2007.07.007, retrieved 15 November 2011
  8. 1 2 3 Hartmann, Katrin (2011), "Clinical aspects of feline immunodeficiency and feline leukemia virus infection", Veterinary Immunology and Immunopathy 143: 190–201, doi:10.1016/j.vetimm.2011.06.003, retrieved 16 November 2011
  9. 1 2 3 Yamamoto, Janet; Missa Sanou; Jeffrey Abbott; James Coleman (2010), "Feline immunodeficiency virus model for designing HIV/AIDS vaccines", Current HIV Research 8: 14–25, doi:10.2174/157016210790416361
  10. ↑ Hosie, MJ; et al. (2009), "Feline immunodeficiency. ABCD guidelines on prevention and management", Journal of Feline Medicine & Surgery 11 (7): 575–84, doi:10.1016/j.jfms.2009.05.006, PMID 19481037.
  11. ↑ LTCI Product Information, T-Cyte Therapeutics, Inc., retrieved 28 July 2012
  12. ↑ T-Cyte Therapeutics, Inc., T-Cyte Therapeutics, Inc., retrieved 28 July 2012
  13. ↑ Beardsley, et al. "Induction of T-Cell Maturation by a Cloned Line of Thymic Epithelium (TEPI) Immunology 80: pp. 6005-6009, (Oct. 1983).
  14. ↑ US patent 7196060, Beardsley, Terry R., "Method to enhance hematopoiesis", published 2005-05-19, issued 2007-03-27
  15. ↑ Levy, J; Crawford, C; Hartmann, K; Hofmann-Lehmann, R; Little, S; Sundahl, E; Thayer, V (2008), "2008 American Association of Feline Practitioners' feline retrovirus management guidelines", Journal of Feline Medicine & Surgery 10 (3): 300–16, doi:10.1016/j.jfms.2008.03.002, PMID 18455463
  16. ↑ Huang, C.; Conlee, D.; Loop, J.; Champ, D.; Gill, M.; Chu, H.J. (2004), "Efficacy and safety of a feline immunodeficiency virus vaccine", Animal Health Research Reviews 5 (2): 295–300, doi:10.1079/AHR200487, PMID 15984343
  17. ↑ Dunham, S.P.; Bruce, J.; Mackay, S.; Golder, M.; Jarrett, O.; Neil, J.C. (2006), "Limited efficacy of an inactivated feline immunodeficiency virus vaccine", Veterinary Record 158 (16): 561–562, doi:10.1136/vr.158.16.561, PMID 16632531
  18. ↑ Kusuhara, H.; Hohdatsu, T.; Okumura, M.; Sato, K.; Suzuki, Y.; Motokawa, K.; Gemma, T.; Watanabe, R.; et al. (2005), "Dual-subtype vaccine (Fel-O-Vax FIV) protects cats against contact challenge with heterologous subtype B FIV infected cats", Veterinary Microbiology 108 (3–4): 155–165, doi:10.1016/j.vetmic.2005.02.014, PMID 15899558
  19. ↑ Pu, R.; Coleman, J.; Coisman, J.; Sato, E.; Tanabe, T.; Arai, M.; Yamamoto, JK. (2005), "Dual-subtype FIV vaccine (Fel-O-Vax FIV) protection against a heterologous subtype B FIV isolate", Journal of Feline Medicine and Surgery 7 (1): 65–70, doi:10.1016/j.jfms.2004.08.005, PMID 15686976
  20. ↑ Levy, J; Crawford, C; Hartmann, K; Hofmann-Lehmann, R; Little, S; Sundahl, E; Thayer, V (2008), "2008 American Association of Feline Practitioners' feline retrovirus management guidelines", Journal of Feline Medicine & Surgery 10 (3): 300–316, doi:10.1016/j.jfms.2008.03.002, PMID 18455463
  21. 1 2 Poeschla, E., Wong-Staal, F., Looney, D. (1998), "Efficient transduction of nondividing cells by feline immunodeficiency virus lentiviral vectors", Nature Medicine 4: 354–357, doi:10.1038/nm0398-354, PMID 9500613
  22. ↑ Harper SQ1, Staber PD, Beck CR, Fineberg SK, Stein C, Ochoa D, Davidson BL (Oct 2006), "Optimization of Feline Immunodeficiency Virus Vectors for RNA Interference", J Virol 80 (19): 9371–80, doi:10.1128/JVI.00958-06, PMC 1617215, PMID 16973543
  23. ↑ Valori CF1, Ning K, Wyles M, Azzouz M (Dec 2008), "Development and applications of non-HIV-based lentiviral vectors in neurological disorders", Curr Gene Ther 8 (6): 406–18, doi:10.2174/156652308786848030, PMID 19075624

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