Feline immunodeficiency virus
Encyclopedia
Feline immunodeficiency virus (FIV) is a lentivirus
that affects domesticated housecats
worldwide and is the causative agent of feline AIDS
. From 2.5% up to 4.4% 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, and cats will test positive for FIV antibodies after vaccination.
FIV was first isolated in 1986 by Pedersen et al. of 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). It has since been identified as an endemic disease
in domestic cat populations worldwide.
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 as well as additional lentiviral genes vif, vpr, and rev. However it does lack the accessory genes tat, vpu, vpx, and nef. The gag polyprotein is proteolytically processed into major capsid proteins while the pol polyprotein is processed into virally encoded enzymes, and env into envelope glycoproteins. 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 codes for surface glycoproteins (SU) and transmembrane glycoproteins (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.
, 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.
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
.
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.
issued a conditional license for a new treatment aid termed Lymphocyte T-Cell Immune Modulator
. Lymphocyte T-Cell Immune Modulator is manufactured by T-Cyte Therapeutics, Inc. LTCI is distributed exclusively by ProLabs Animal Health, a division of AgriLabs, LTD.
Lymphocyte T-Cell Immune Modulator 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 Immune Modulator is a potent regulator of CD-4 lymphocyte
production and function. It has been shown to increase lymphocyte numbers and Interleukin 2
production in animals.
Lymphocyte T-Cell Immune Modulator 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.
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, neither can infect the other's usual host: 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.
Consensus in America on whether there is a need to euthanize FIV infected cats has not been established. The American Associations of Feline Practitioners, as well as many feral cat organizations, recommend against euthanizing FIV+ cats, or even spending funds to test for the virus, as spaying or neutering cats seems to effectively control transmission - as neutered cats are less likely to engage in territorial fights. 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 . 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 not non-existent risk.
FIV infects other feline species, and in fact is endemic in some large wild cats, such as Africa
n lion
s. Unlike domestic cats, these species do not necessarily exhibit symptoms, perhaps because they have developed evolution
ary mutation
s that confer resistance.
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 the number of CD4+ 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).
Risk factors for infection are male sex, adulthood, and outdoor access. One case study conducted in Sao 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 .
for gene therapy. Like other lentivirus vectors, FIV vectors integrate into the chromosome of the host which provides long-term heritable gene expression. Furthermore the vectors can be used on dividing and non-dividing cells. 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.
Lentivirus
Lentivirus is a genus of slow viruses of the Retroviridae family, characterized by a long incubation period...
that affects domesticated housecats
Cat
The cat , also known as the domestic cat or housecat to distinguish it from other felids and felines, is a small, usually furry, domesticated, carnivorous mammal that is valued by humans for its companionship and for its ability to hunt vermin and household pests...
worldwide and is the causative agent of feline AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
. From 2.5% up to 4.4% of cats worldwide are infected with FIV. FIV differs taxonomically from two other feline retroviruses, feline leukemia virus
Feline leukemia virus
Feline leukemia virus is a retrovirus that infects cats. FeLV can be transmitted between infected cats when the transfer of saliva or nasal secretions is involved. If not defeated by the animal’s immune system, the virus can be lethal...
(FeLV) and feline foamy virus (FFV), and is more closely related to human immunodeficiency virus HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
. 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
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
is available although its efficacy remains uncertain, and cats will test positive for FIV antibodies after vaccination.
FIV was first isolated in 1986 by Pedersen et al. of the UC Davis School of Veterinary Medicine
UC Davis School of Veterinary Medicine
The University of California, Davis, School of Veterinary Medicine, is the largest veterinary school in the United States. Established in 1948, the school is the primary health resource for California's various animal populations. The school is ranked 2nd for veterinary schools in the country...
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). It has since been identified as an endemic disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
in domestic cat populations worldwide.
Structure
FIV is structured liked other lentiviruses, which cause immune deficiency syndromes in mammals. The virion has a diameter from 80 to 100 nanometers and is pleomorphic. The viral envelope also has surface projections that are small, 8nm, and evenly cover the surface.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 as well as additional lentiviral genes vif, vpr, and rev. However it does lack the accessory genes tat, vpu, vpx, and nef. The gag polyprotein is proteolytically processed into major capsid proteins while the pol polyprotein is processed into virally encoded enzymes, and env into envelope glycoproteins. 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 codes for surface glycoproteins (SU) and transmembrane glycoproteins (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.
Transmission
The primary modes of FIV transmission are deep bite wounds and scratches, where the infected cat's saliva enters the other cat's bloodstream. FIV may also be transmitted from pregnant females to their offspring in utero. This differs from FeLVFELV
FELV may refer to:* Functional Extra Low Voltage, see Extra low voltage#Functional Extra Low Voltage * Feline leukemia virus, 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.
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
Seroconversion
Seroconversion is the development of detectable specific antibodies to microorganisms in the blood serum as a result of infection or immunization. Serology is used to determine antibody positivity...
, 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
Animal euthanasia
Animal euthanasia is the act of putting to death painlessly or allowing to die, as by withholding extreme medical measures, an animal suffering from an incurable, especially a painful, disease or condition. Euthanasia methods are designed to cause minimal pain and distress...
.
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.
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: ) 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. The vaccine was shown to be moderately protective (82% of cats were protected) against subtype A FIV, but a later study showed it to offer no protection against subtype A. It has shown 100% effectiveness against two different subtype B FIV strains. 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.Approved treatment
In 2006, the United States Department of AgricultureUnited States Department of Agriculture
The United States Department of Agriculture is the United States federal executive department responsible for developing and executing U.S. federal government policy on farming, agriculture, and food...
issued a conditional license for a new treatment aid termed Lymphocyte T-Cell Immune Modulator
Lymphocyte T-Cell Immune Modulator
Lymphocyte T-Cell Immune Modulator is an immune regulating polypeptide manufactured by T-Cyte Therapeutics and distributed by . Lymphocyte T-Cell Immune Modulator is a potent regulator of CD-4 lymphocyte production and function. It has been shown to increase lymphocyte numbers and Interleukin-2 ...
. Lymphocyte T-Cell Immune Modulator is manufactured by T-Cyte Therapeutics, Inc. LTCI is distributed exclusively by ProLabs Animal Health, a division of AgriLabs, LTD.
Lymphocyte T-Cell Immune Modulator 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
Lymphocytopenia
Lymphocytopenia, or lymphopenia, is the condition of having an abnormally low level of lymphocytes in the blood. Lymphocytes are a white blood cell with important functions in the immune system...
, opportunistic infection
Opportunistic infection
An opportunistic infection is an infection caused by pathogens, particularly opportunistic pathogens—those that take advantage of certain situations—such as bacterial, viral, fungal or protozoan infections that usually do not cause disease in a healthy host, one with a healthy immune system...
, anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
, granulocytopenia, or thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
. The absence of any observed adverse events in several animal species, suggests that the product has a very low toxicity profile.
Lymphocyte T-Cell Immune Modulator is a potent regulator of CD-4 lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
production and function. It has been shown to increase lymphocyte numbers and Interleukin 2
Interleukin 2
Interleukin-2 is an interleukin, a type of cytokine immune system signaling molecule, which is a leukocytotrophic hormone that is instrumental in the body's natural response to microbial infection and in discriminating between foreign and self...
production in animals.
Lymphocyte T-Cell Immune Modulator is a single chain polypeptide. It is a strongly cationic glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
, and is purified with cation exchange resin. Purification of protein from bovine-derived stromal cell
Stromal cell
In cell biology, stromal cells are connective tissue cells of any organ, for example in the uterine mucosa , prostate, bone marrow, and the ovary. They are cells that support the function of the parenchymal cells of that organ...
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.
Effects
FIV can attack the immune systemImmune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
of cats, much like the human immunodeficiency virus
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
(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, neither can infect the other's usual host: 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.
Consensus in America on whether there is a need to euthanize FIV infected cats has not been established. The American Associations of Feline Practitioners, as well as many feral cat organizations, recommend against euthanizing FIV+ cats, or even spending funds to test for the virus, as spaying or neutering cats seems to effectively control transmission - as neutered cats are less likely to engage in territorial fights. 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 . 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 not non-existent risk.
FIV infects other feline species, and in fact is endemic in some large wild cats, such as Africa
Africa
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
n lion
Lion
The lion is one of the four big cats in the genus Panthera, and a member of the family Felidae. With some males exceeding 250 kg in weight, it is the second-largest living cat after the tiger...
s. Unlike domestic cats, these species do not necessarily exhibit symptoms, perhaps because they have developed evolution
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
ary mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s that confer resistance.
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)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 the number of CD4+ 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).
Disease Stages
FIV progresses through similar stages to HIV in humans. The initial stage, or acute phase, is accompanied by mild symptoms such as fever, lethargy, anorexia, pyrexia, and lymphadenopathy . This initial stage is fairly short and is followed by the asymptotic 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 .Symptoms
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 numbers of FIV-infected kittens and adolescents . .Risk factors for infection are male sex, adulthood, and outdoor access. One case study conducted in Sao 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 .
Viral vector
FIV has potential to be used as a viral vectorViral vector
Viral vectors are a tool commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism or in cell culture . Viruses have evolved specialized molecular mechanisms to efficiently transport their genomes inside the cells they infect...
for gene therapy. Like other lentivirus vectors, FIV vectors integrate into the chromosome of the host which provides long-term heritable gene expression. Furthermore the vectors can be used on dividing and non-dividing cells. FIV vectors could potentially be used to treat neurological disorders like Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
, and have already been used for transfer RNAi which may find use as gene therapy for cancer.