Feline immunodeficiency virus

Feline immunodeficiency virus (FIV) is a Lentivirus that affects cats worldwide, with 2.5% to 4.4%[1][2] of felines being infected. 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" redirects here. For the Federazione Italiana Vela, see Italian Sailing Federation.
Feline immunodeficiency virus
Virus classification
(unranked): Virus
Realm: Riboviria
Kingdom: Pararnavirae
Phylum: Artverviricota
Class: Revtraviricetes
Order: Ortervirales
Family: Retroviridae
Genus: Lentivirus
Species:
Feline immunodeficiency virus

FIV was first isolated in 1986 by Niels Pedersen 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.[4] It has since been identified in domestic cats.[5]

Effects

FIV compromises the immune system of cats by infecting many cell types, 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. The rate of occurrence in cats is at less than 5%; in humans with HIV, this percentage is estimated to be over 50%.

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 deep bite wounds, where the virus present in the infected cat's saliva enters the body tissues of another cat. FIV+ cats can share water bowls, pellet bowls, eat from the same bowl of wet food, and use the same litter box with low danger of transmitting the disease. A vigilant pet owner who treats secondary infections can allow an infected cat to live a reasonably long life. The chance that an FIV-infected cat will pass the virus to other cats within a household is low, unless there is fighting between cats, or wounds present that could allow entry of the virus from infected to non-infected cat.

Newborn kittens may test positive for up to six months and most thereafter will gradually test negative. It is thought that this is due to antibodies transferred to the kittens via the mother's milk. However these antibodies are transient so subsequent testing will be negative. Once they have received vaccinations against FIV, they will, in the future, always test positive, as the various blood tests detect and show the antibodies that have developed in response to the vaccination.

FIV is known in other feline species, and in fact is endemic in some large wild cats, such as African lions. Three main clades of FIV are recognized as of 2006, FIV-Ple (lion), FIV-Fca (domestic cat), and FIV-Pco (puma).[6] The host boundaries are usually well-kept due to the limited types of APOBEC3 enzymes viral Vif can neutralize.[7]

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 Association of Feline Practitioners (an organization in the United States), as well as many feral cat organizations, recommends 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).[8]

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.[9] 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 nonhomologous recombination. Once integrated into the host cell's genome, the virus can lay dormant in the asymptomatic stage for extended periods of time without being detected by the immune system or can cause lysis of the cell.[10][11]

CD134 is predominantly 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).[12]

Transmission

The primary mode of transmission is via deep bite wounds, in which the infected cat's saliva enters the other cat's tissues. 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][12] This differs from FeLV, which may be spread by more casual, non-aggressive contact, such as mutual grooming and sharing of food bowls.

Risk factors for infection include male sex, adulthood, and outdoor access. One case study conducted in São Paulo found that 75 percent of FIV-infected cats were males. Higher rates of infection in males than females occurs due to biting being more frequently engaged in by males defending their territory.[11]

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.[12] 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), wherein the cat is extremely susceptible to secondary diseases that inevitably are the cause of death.[11]

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. This testing identifies those cats that carry the FIV antibody but 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 eight 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 lives owing 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.[13]

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).[14] Lymphocyte T-Cell Immunomodulator is manufactured and distributed exclusively by T-Cyte Therapeutics, Inc.[15]

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.[16] It has been shown to increase lymphocyte numbers and Interleukin 2 production in animals.[17] It is a single chain polypeptide and 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 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.[18] The vaccine was shown to be moderately protective (82% of cats were protected) against subtype A FIV,[19] but a later study showed it to offer no protection against sub type A.[20] It has shown 100% effectiveness against two different subtype B FIV strains.[21][22] 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.[23]

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.[10]

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.[10]

Lentiviral vector

Like HIV-1, FIV has been engineered into a viral vector for gene therapy.[24] 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.[24][25] 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.[26]

Comparison with feline leukemia virus

FIV and feline leukemia virus (FeLV) are sometimes mistaken for one another though the viruses differ in many ways. Although they are both in the same retroviral subfamily (orthoretrovirinae), they are classified in different genera (FeLV is a gamma-retrovirus and FIV is a lentivirus like HIV-1). Their shapes are quite different: FeLV is more circular while FIV is elongated. The two viruses are also quite different genetically, and their protein coats differ in size and composition. Although many of the diseases caused by FeLV and FIV are similar, the specific ways in which they are caused also differs. Also, while the feline leukemia virus may cause symptomatic illness in an infected cat, an FIV infected cat can remain completely asymptomatic its entire lifetime.

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See also

References
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