Leukemia virus, feline

Feline leukemia virus

Feline leukemia virus (FeLV) is a retrovirus that infects cats. As a retrovirus, the genetic information of FeLV is carried by RNA instead of DNA. FeLV is usually transmitted between infected cats when the transfer of saliva or nasal secretions is involved, for example when sharing a feeding dish. If not defeated by the animal’s immune system, the virus can be lethal.

The disease is a virus, not a cancer. The name stems from the fact that the first disease associated with the virus was a form of leukemia. By the time it was discovered that the virus was not the same as leukemia, the misnomer had already found its way into the vocabulary of pet owners.

Transmission

Cats infected with FeLV can serve as sources of infection. Cats pass the virus between themselves through saliva and close contact, by biting another cat, through a litter box or food dish used by an infected cat, and from milk during nursing. Transmission can also take place from an infected mother cat to her kittens, either before they are born or while they are nursing.

The virus can survive only about 2 hours in a dry environment, and about 48 hours in a damp environment (such as a litter box).

FeLV causes immunosuppression in pet cats, and there is also evidence for existence of the virus in larger wild cat populations also (e.g. Lynx, Cheetah, and Lion). Overwhelming epidemiologic evidence suggests FeLV is not transmissible to either humans or dogs. This statement is based on the fact that approximately one pet dog in five lives with a cat, and all pet cats live with humans (some 60 million pet cats in the USA). It is species-specific, and does not infect other animals, such as dogs (in fact, there is apparently no canine version of this disease at all).

Approximately 0.5% of pet cats are persistently infected with FeLV, but many more pet cats (>35%) have specific IgG antibodies which indicate prior exposure and subsequent development of immunity instead of infection. Transmission of FeLV is mainly via saliva and friendly behaviours, such as sharing feeding bowls and mutual grooming (as distinct from fighting and biting).

There is strong evidence kittens under 4 months of age are susceptible to infection, but by eight months are resistant - hence it is a good idea to keep young pet kittens indoors where virus exposure is minimal or non-existent until about 8 months of age.

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.

The disease's effect has a wide range: the cat can fight off the infection and becoming totally immune; can become a carrier (like a Typhoid Mary) that never gets sick itself, but infects other cats; to a mid-level case in which the cat has a compromised immune system.

Four subgroups of FeLV exist: A; B; C, and T, but only subgroup A is transmissible between cats. The other subgroups arise de novo and as results of recombination with an endogenous DNA feline sequence. Hence, there is very good evidence this virus is quite ancient, and may well have evolved more than one time over the last 10,000,000 years.

Progression

There are many possible outcomes as to how successfully the cat’s immune system will react to the virus. About forty percent of cats extinguish the virus. Sixteen percent fight it off due to minimal exposure to it. The other twenty-four percent resist the virus at phase four, which will be described later. All of this usually occurs between sixteen to eighteen weeks after the FeLV infection begins. About twenty percent are able to put the virus into a latent stage, in which the virus will remain until the cat becomes stressed causing the FeLV to re-emerge. About five to ten percent of cats go through a sequestered stage in which viremia is limited, intermittent, or absent altogether. Approximately thirty percent of cats go through the disease from start to finish, normally resulting in death.

Once the virus has entered the cat, there are six phases to a FeLV infection:

Phase one is when the virus enters the cat, usually through the pharynx where it infects the epithelial cells and infects the tonsillar B-lymphocytes and macrophages. These white blood cells then filter down to the lymph nodes and begin to replicate.
In phase two, the virus enters the blood stream and begins to distribute throughout the body.
Phase three starts when the lymphoid system (produces antibodies to attack infected and cancerous cells) becomes infected with further distribution throughout the body.
Phase four is the main point in the infection, where the virus can take over the body's immune system cause viremia. During this phase the hemolymphatic system and intestines become infected.
If the cat's immune system does not fight off the virus, then it goes onto phase five where the bone marrow 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 (white blood cells), and sometimes lymphocytes, monocytes (white blood cell formed in the bone marrow), and eosinophils (another white blood cell).
At phase 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.

Cats diagnosed as persistently infected by ELISA testing may die within a few months or may remain asymptomatic for up to 4 years. The fatal diseases are leukemias, lymphomas, and non-regenerative Anemias. 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 and/or FIV infections.

Prevention

Vaccines for FeLV are available, though no currently available vaccine offers 100% protection from the virus. Serious side effects have also been reported as a result of FeLV vaccination; in particular, a small percentage of cats who received FeLV vaccines subsequently developed vaccine-associated sarcomas, 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 adjuvants in the vaccines.

Merial produces a recombinant vaccine consisting of canarypox virus carrying FeLV gag and env genes (sold as PUREVAX FeLV in the USA 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.

Since the virus is very weak and dies within two hours in a dry environment, if you can keep the litterbox from remaining damp between uses, the incidence of transmission will drop considerably. One method is to clean all damp litter out of a standard box after each use; however, this is sometimes not practical.

Another option is a specialized litterbox called the "SmartCatBox" (information located at www.SmartCatBox.com), a three-part litterbox that uses either a ground corncob or safflower seed litter in a slotted top unit, which allows the liquid to drain into a reservoir that is emptied regularly. The litter material air-dries quickly, thus killing the virus quickly.

This litterbox was originally designed for diabetic cats, to allow regular testing of the sugar level in the cat's system. By coincidence, the box also helps prevent FeLV infection between household cats. (The safflower seed litter is actually better, as it has a smoother surface and is easier on a cat's feet; alternate litterbox material includes shelled corn; you just have to get the cat used to using the new material, but most cats will take to it very easily.)

Viral structure

Feline Leukemia Virus (FeLV) is an RNA retrovirus or oncornavirus first described by W. Jarrett (et al, Nature 202:566) at University of Glasgow, School Veterinary Medicine, in 1964. The virus comprises 5' and 3' LTR's and three genes: Gag (structural), Pol (enzymes) and Env (envelope and transmembrane); the total genome is about 9,600 base-pairs.

See the entry on retroviruses for more details on the life cycle of FeLV.

Suggested Therapies and Treatments

A FeLV infected cat may not actually display any sign of sickness. The virus does not actually kill the cat; it compromises the immune system. This makes it very easy for the cat to contract other infections that run out of control: a simple nail injury can become a full-blown, out-of-control infection. It is these infections and the likelihood of cancer that are the main treatment problem. A FeLV-positive cat can die at six months, two years or 10 years after the initial infection with the virus.

Because cats normally may not appear to be sick until they are in an advanced state of illness, it is vital that cat owners pay close attention to their pets' day-to-day condition. Cats should be examined regularly for painful or swollen areas. Any cat showing these symptoms should be examined by a veterinarian. Treatment may consist of a course of antibiotics for bacterial infections, sometimes for a few weeks due to the difficulty of eliminating the infection.

It may be advisable to take away any scratching pads and posts: when cats sharpen their claws, they strain the base of their claws, causing the skin to open up a bit. This is enough to let in the bacteria that will infect the cat.

Treatment Options

In 2006, the United States Department of Agriculture 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. and exclusively sold by IMULAN BioTherapeutics, LLC.

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.

The cat should receive as much immune-system support as possible. Nutritional supplements that may support the cat's immune system include: colostrom (a milk product), Chinese mushroom extracts, plant-based extracts (purple coneflower, for example), and cat vitamins.

A FeLV-positive cat may also have persistent gingivitis and other dental problems (persistent gingivitis is a prime symptom of FeLV and FIV).

The use of interferon is recommended for use against FeLV. Interferon alpha is available in the United States. 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 improvement in mortality rates; in non-anaemic cats, mortality rate of 50% was reduced by approximately 20% following treatment.

The drug is quite expensive dependent on body-weight, but will be covered by most pet insurers.

The use of inteferons are not recommended for cats currently using steroids for symptomatic treatment. A 2 week withdrawal period is recommended before starting treatment, and steroids should ideally not be used at any point after the treatment, as they will effectively reverse the efficacy of the drug (inteferon-ω simulates natural leukocyte response, and steroids will greatly hamper this).

For American pet owners, one way to deal with leukemia or anemia associated with FeLV is blood transfusions. It is also recommended that the cat undergo a battery of tests such as a bone marrow aspiration, abdominal ultrasound, chest x-ray, or thoractic endoscopy. With the results from these, the disease's effects may be seen on the viscera and any cancerous tumours arising from the disease may be taken care of. Following transfusion, it is important to keep the cat on antibiotics and steroids.

Comparison with FIV

FeLV and Feline immunodeficiency virus are in the same family, and are sometimes mistaken for one another. However, the viruses differ in many ways. 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.

Comparison with HIV

Dr. Don Francis at the Center for Disease Control in Atlanta theorized that AIDS was caused by a sexually transmitted virus on the model of FeLV. As director of CDC's AIDS Laboratory Activities, he worked closely with the Institut Pasteur to eventually demonstrate that HIV was the cause of AIDS.