Feline leukemia virus (FeLV) is a

retrovirus A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase ...

that infects

cat The cat (''Felis catus'') is a domestic species of small carnivorous mammal. It is the only domesticated species in the family Felidae and is commonly referred to as the domestic cat or house cat to distinguish it from the wild members of ...

s. FeLV can be transmitted from infected cats when the transfer of saliva or nasal secretions is involved. If not defeated by the animal's

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

, the virus weakens the cat's immune system, which can lead to diseases which can be lethal. Because FeLV is cat-to-cat contagious, FeLV+ cats should only live with other FeLV+ cats. FeLV is categorized into four subgroups, A, B, C and T. An infected cat has a combination of FeLV-A and one or more of the other subgroups. Symptoms, prognosis and treatment are all affected by subgroup. FeLV+ cats often have a shorter lifespan, but can still live "normal", healthy lives.

Signs and symptoms

The signs and symptoms of infection with feline leukemia virus are quite varied and include

loss of appetite Anorexia is a medical term for a loss of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others i ...

, poor coat condition, anisocoria (uneven pupils), infections of the skin, bladder, and respiratory tract, oral disease,

seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...

lymphadenopathy Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cli ...

(swollen lymph nodes),

skin lesions A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this sy ...

fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...

weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other conn ...

stomatitis Stomatitis is inflammation of the mouth and lips. It refers to any inflammatory process affecting the mucous membranes of the mouth and lips, with or without oral ulceration. In its widest meaning, stomatitis can have a multitude of different cau ...

gingivitis Gingivitis is a non-destructive disease that causes inflammation of the gums. The most common form of gingivitis, and the most common form of periodontal disease overall, is in response to bacterial biofilms (also called plaque) that is attached ...

, litter box avoidance,

pancytopenia Pancytopenia is a medical condition in which there is significant reduction in the number of almost all blood cells (red blood cells, white blood cells, platelets, monocytes, lymphocytes, etc.). If only two parameters from the complete blood coun ...

, recurring bacterial and viral illnesses,

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...

and

jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...

. Asymptomatic carriers will show no signs of disease, often for many years.

Progression

The disease has a wide range of effects. The cat can fight off the infection and become totally immune, can become a healthy carrier that never gets sick itself but can infect other cats, or a mid-level case in which the cat has a compromised immune system. Nevertheless, the development of lymphomas is considered the final stage of the disease. Although it is thought that virus protein has to be present to induce lymphomas in cats, newer evidence shows that a high percentage of FeLV-Antigen negative lymphomas contain FeLV-DNA, indicating a "hit-and-run" mechanism of virus-induced tumor development. Once the virus has entered the cat, there are six stages to a FeLV infection: * Stage One: The virus enters the cat, usually through the pharynx where it infects the epithelial cells and infects the tonsilar B-lymphocytes and macrophages. These white blood cells then filter down to the lymph nodes and begin to replicate. * Stage Two: The virus enters the blood stream and begins to distribute throughout the body. * Stage Three: The lymphoid system (which produces antibodies to attack infected and cancerous cells) becomes infected, with further distribution throughout the body. * Stage Four: The main point in the infection, where the virus can take over the body's immune system and cause viremia. During this stage the hemolymphatic system and intestines become infected. If the cat's immune system does not fight off the virus, then it progresses to: * Stage Five: The

bone marrow Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...

becomes infected. At this point, the virus will stay with the cat for the rest of its life. In this phase, the virus replicates and is released four to seven days later in infected

neutrophils Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...

, and sometimes lymphocytes,

monocytes Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also infl ...

, and

eosinophils Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...

(all white blood cells formed in the bone marrow). * Stage Six: The cat's body is overwhelmed by infection and mucosal and glandular epithelial cells (tissue that forms a thin protective layer on exposed bodily surfaces and forms the lining of internal cavities, ducts, and organs) become infected. The virus replicates in epithelial tissues including salivary glands, oropharynx, stomach, esophagus, intestines, trachea, nasopharynx, renal tubules, bladder, pancreas, alveolar ducts, and sebaceous ducts from the muzzle.

Transmission

Cat The cat (''Felis catus'') is a domestic species of small carnivorous mammal. It is the only domesticated species in the family Felidae and is commonly referred to as the domestic cat or house cat to distinguish it from the wild members of ...

s infected with FeLV can serve as sources of infection of FeLV-A. Cats can pass the virus between themselves through saliva and close contact, by biting another cat, and (rarely) through a litter box or food dish used by an infected cat. Once a cat has been infected with FeLV-A, additional mutated forms of the original FeLV-A virus may arise, as may FeLV subgroups B, C and T. In addition to domestic cats, some other members of

Felidae Felidae () is the family of mammals in the order Carnivora colloquially referred to as cats, and constitutes a clade. A member of this family is also called a felid (). The term "cat" refers both to felids in general and specifically to the ...

are now threatened by FeLV (e.g.

lynx A lynx is a type of wild cat. Lynx may also refer to: Astronomy * Lynx (constellation) * Lynx (Chinese astronomy) * Lynx X-ray Observatory, a NASA-funded mission concept for a next-generation X-ray space observatory Places Canada * Lynx, Ontar ...

and

Florida panther The Florida panther is a North American cougar (''P. c. couguar'') population in South Florida. It lives in pinelands, tropical hardwood hammocks, and mixed freshwater swamp forests. It is known under a number of common names including Costa R ...

). Overwhelming

epidemiologic Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in a defined population. It is a cornerstone of public health, and shapes policy decisions and evidenc ...

evidence suggests FeLV is not transmissible to either humans or dogs. Approximately 0.5% of pet cats are persistently infected with FeLV, but many more pet cats (>35%) have specific

IgG Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...

antibodies which indicate prior exposure and subsequent development of

immunity Immunity may refer to: Medicine * Immunity (medical), resistance of an organism to infection or disease * ''Immunity'' (journal), a scientific journal published by Cell Press Biology * Immune system Engineering * Radiofrequence immunity desc ...

instead of

infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...

. FeLV is highly infectious. Kittens can be born with it, having contracted it from their mother while ''in utero''. Infection is far higher in city cats, stray or owned, than in rural cats: this is entirely due to the amount of contact the cats have with each other.

Diagnosis and prognosis

Testing for FeLV is possible with

ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presence ...

tests that look for viral

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

s, free particles found in the bloodstream. These ELISA tests use blood samples most often, but can also use saliva or eye secretions. The sample is added to a container or dish that contains the antibodies to the viral antigens. If the antigens are present in the sample, the antibodies will bind to them and an indicator on the test will change color. These give a definitive diagnosis, but it cannot differentiate between acute or persistent infections. Therefore, it is recommended that the cat be retested in three to four months after the positive result to determine if the virus has been cleared from the body. Diagnosis can also be made by reference lab testing, using an

immunofluorescence Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on microbiological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specif ...

(IFA) test. The IFA test uses a blood sample and will detect the virus once it is in the bone marrow by detecting the virus's presence in white blood cells. IFA testing will not give positive results for transient, primary infections - the infection must be persistent to get a positive result on this test. Other than ELISA and IFA testing, routine laboratory blood work may show changes that indicate infection but cannot be used as a definitive diagnosis. There may be blood cell count changes like

leukopenia Leukopenia () is a decrease in the number of leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of inf ...

, decreased Packed Cell Volume (PCV) and Total Protein (TP) levels due to

, hemoconcentration and hypoglycemia due to vomiting and diarrhea, electrolyte imbalance caused by dehydration and anorexia, and recurrent urinary tract infections.Johnson, A. (2014). Small Animal Pathology for Veterinarian Technicians. Hoboken: Wiley Blackwell. Cats diagnosed as persistently infected by

testing may die within a few months or may remain asymptomatic for longer; median survival time after diagnosis is 2.5 years. FeLV is categorized into four subgroups. * FeLV-A is responsible for the

immunosuppression Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...

characteristic of the disease. The vast majority of cats with FeLV has FeLV-A. An exception was reported in 2013. * FeLV-B causes an additional increase in the incidence of tumors and other abnormal tissue growths. About half of FeLV infected cats have FeLV-B. It forms by recombination of FeLV-A and cat endogenous FeLV (enFeLV). * FeLV-C causes severe anemia. Approximately 1% of FeLV infected cats have FeLV-C. It forms by mutation of FeLV-A. * FeLV-T leads to lymphoid depletion and immunodeficiency. It forms by mutation of FeLV-A. The fatal diseases are

leukemias Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...

lymphomas Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlar ...

, and non-regenerative

anemias Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...

. Although there is no known cure for the virus infection, in 2006 the United States Department of Agriculture approved Lymphocyte T-Cell Immunomodulator as a treatment aid for FeLV (see Treatment).

Prevention

Three types of vaccines for FeLV are available: an

adjuvant In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy or potency of certain drugs. Specifically, the term can refer to: * Adjuvant therapy in cancer management * Analgesic ...

ed killed virus noninfectious vaccine, an

ed subunite vaccine and a nonadjuvanted canarypox virus-vectored recombinant infectious vaccine (

ATCvet The Anatomical Therapeutic Chemical (ATC) Classification System is a drug classification system that classifies the active ingredients of drugs according to the organ or system on which they act and their therapeutic, pharmacological and chemical p ...

code QI066AA01 and various combination vaccines), though no currently available vaccine offers 100% protection from the virus. Vaccination is recommended for high-risk cats: those that have access to the outdoors, feral cats, cats that do not have the virus but live with an infected cat, multicat households, and cats with an unknown status, such as cats in catteries and shelters. Serious side effects have also been reported as a result of FeLV vaccination; in particular, a small percentage of cats who received the adjuvanted killed virus vaccine developed

vaccine-associated sarcoma A vaccine-associated sarcoma (VAS) or feline injection-site sarcoma (FISS) is a type of malignancy, malignant tumor found in cats (and often, dogs and ferrets) which has been linked to certain vaccines. VAS has become a concern for veterinarians an ...

s, an aggressive tumour, at the injection site. The development of sarcomas with the use of the old FeLV and other vaccines may be due to the inflammation caused by

aluminium Aluminium (aluminum in American and Canadian English) is a chemical element with the symbol Al and atomic number 13. Aluminium has a density lower than those of other common metals, at approximately one third that of steel. I ...

adjuvants In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy or potency of certain drugs. Specifically, the term can refer to: * Adjuvant therapy in cancer management * Analgesi ...

in the vaccines.

Merial Boehringer Ingelheim Animal Health is a multinational animal health company, formed in January 2017 when Merial was acquired by Boehringer Ingelheim and merged with Boehringer Ingelheim's existing animal health assets. Overview In August 1997, ...

produces a recombinant vaccine consisting of

canarypox Canarypox virus (CNPV) is an ''Avipoxvirus'' and etiologic agent of canarypox, a disease of wild and captive birds that can cause significant losses. Canarypox can enter human cells, but it cannot survive and multiply in human cells. There is a ...

virus carrying FeLV ''gag'' and ''env'' genes (sold as PUREVAX FeLV in the US and Eurifel FeLV in Europe). This is thought to be safer than the old vaccine as it does not require an adjuvant to be effective. Although this is a live virus, it originates from a bird host and so does not replicate in mammals.

Viral structure

Feline leukemia virus (FeLV) is an RNA virus in the subfamily Oncovirinae belonging to the

Retroviridae A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase e ...

family. The

virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...

comprises 5' and 3' LTRs and three genes: Gag (structural), Pol (enzymes) and Env (envelope and transmembrane); the total

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

is about 9,600

base pairs A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...

. See the entry on

es for more details on the life cycle of FeLV.

Treatment

Approved US treatment

In 2006, the

United States Department of Agriculture The United States Department of Agriculture (USDA) is the United States federal executive departments, federal executive department responsible for developing and executing federal laws related to farming, forestry, rural economic development, ...

issued a conditional license for a new treatment aid termed

Lymphocyte T-Cell Immunomodulator Lymphocyte T-cell immunomodulator (LTCI) is an immune regulating polypeptide, which is a potent regulator of CD-4 lymphocyte production and function. It increases lymphocyte numbers and interleukin-2 (IL-2) production in animals. It is extracted fro ...

(LTCI). Lymphocyte T-Cell Immunomodulator is manufactured and distributed exclusively by T-Cyte Therapeutics, Inc. 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 Feline immunodeficiency virus (FIV) is a '' Lentivirus'' that affects cats worldwide, with 2.5% to 4.4% of felines being infected. FIV was first isolated in 1986, by Niels C Pedersen and Janet K. Yamamoto at the UC Davis School of Veterina ...

(FIV), and the associated symptoms of

lymphocytopenia Lymphocytopenia 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. It is also called lymphopenia. The opposite is lymphocytosis, which ...

opportunistic infection An opportunistic infection is an infection caused by pathogens (bacteria, fungi, parasites or viruses) that take advantage of an opportunity not normally available. These opportunities can stem from a variety of sources, such as a weakened immune ...

granulocytopenia Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They hav ...

, or

thrombocytopenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients an ...

. 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 A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...

production and function. It has been shown to increase lymphocyte numbers and

Interleukin 2 Interleukin-2 (IL-2) is an interleukin, a type of cytokine signaling molecule in the immune system. It is a 15.5–16 kDa protein that regulates the activities of white blood cells (leukocytes, often lymphocytes) that are responsible for ...

production in animals. Lymphocyte T-Cell Immunomodulator is a single chain

polypeptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A p ...

. It is a strongly cationic

glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...

, and is purified with cation exchange resin. Purification of protein from bovine-derived

stromal cell Stromal cells, or mesenchymal stromal cells, are differentiating cells found in abundance within bone marrow but can also be seen all around the body. Stromal cells can become connective tissue cells of any organ, for example in the uterine mucos ...

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.

Approved European treatment

Interferon-ω (omega) is sold in Europe at least under the name Virbagen Omega and manufactured by Virbac. When used in treatment of cats infected with FeLV in non-terminal clinical stages (over the age of 9 weeks) there have been substantial improvements in mortality rates; in non-anemic cats, mortality rate of 50% was reduced by approximately 20% following treatment.

History

FeLV was first described in cats in 1964. The disease was originally associated with leukemia; however, it was later realized that the initial signs are generally

and

. The first diagnostic test became available in 1973, which led to a "test and elimination" regime, dramatically reducing the number of infected cats in the general population. The first vaccine became available in 1986.

Comparison with feline immunodeficiency virus

FeLV and

(FIV) 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 differ. Also, while the feline leukemia virus may cause symptomatic illness in an infected cat, an

FIV Feline immunodeficiency virus (FIV) is a ''Lentivirus'' that affects cats worldwide, with 2.5% to 4.4% of felines being infected. FIV was first isolated in 1986, by Niels C Pedersen and Janet K. Yamamoto at the UC Davis School of Veterinary ...

infected cat can remain completely asymptomatic its entire lifetime.

References

* B. Zharkoy, A. Zolototrubov, D. Fedosov. "Intensity of free radical processes in limphocytes at BLV and FeLV". ''Journal of Animal Science''. XLII,5/2005, p. 272-276.

External links

Lymphocyte T-Cell Immunomodulator (LTCI)

Feline Leukemia Virus (FeLV) from Veterinary Partner

Feline leukemia Treatments and Support

Feline Leukemia Virus from Cornell Feline Health Center

Feline Leukemia Virus Infection (FeLV) in Cats

{{Taxonbar, from=Q769471 Cat diseases Gammaretroviruses Animal viral diseases