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. There is currently no known cure for infection.

Transmission
Cats infected with FeLV serve as sources of infection. Cats pass the virus between themselves through mutual grooming (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 is very weak, and can survive only about 2 hours in a dry environment, and about 48 hours in a damp environment (such as a litter box).

The disease is actually a virus, not a cancer. The name actually stems from the fact that the first disease associated with the virus was a form of leukemia. Once it was discovered that the virus was not the same as the leukemia, the name had stuck.

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. There is no known cure for the virus infection and no known palliative pharmaceutical therapy. Vaccines for FeLV are available, but their efficacy remains unproven and serious side effects have been reported.

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.

The replication process of the FeLV virus is fairly straightforward. First the virus attaches to receptors on surface of the target cell. Then the virus penetrates the cell membrane, sheds its envelope and capsid, and releases its single stranded RNA and reverse transcriptase. Reverse transcriptase, with the help of the cat's cellular enzymes, makes the ssRNA into double stranded DNA. The dsDNA circulates and integrates into the nucleus and attempts to incorporate into the cat's chromosomes. If the viral DNA is successful in incorporating into the cat's DNA it transcribes to mRNA. The new viral RNA, proteins, and reverse transcriptase are synthesized, assembled, and then bud from the plasma membrane as a new FeLV virus to infect another cell. When the dsDNA is integrated into the nucleus it can have four possible effects: productive infection, latent infection, insertional mutagenesis (in which the viral DNA is incorporated into a critical part of the DNA and mutates the cell), and finally failure of integration (where viral DNA accumulates in the cell and is toxic to it).

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.

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-ω is recommended for use against FeLV. Interferon-ω 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, the current way to "deal" with FeLV (active leukemia infections) is blood transfusions for anaemic cats. 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.