FeLV is an enveloped RNA virus that belongs to the genus Gammaretrovirus of the family Retroviridae. FeLV infection remains an important cause of mortality in domestic cats through its ability to cause immune suppression, bone marrow disorders, and hematopoietic neoplasia. FeLV also causes disease in wild felids such as the highly endangered Iberian lynx.
FeLV infection progresses more rapidly than FIV infection and is more pathogenic, so most cats that develop progressive infections ultimately die of FeLV-related disease. However, in contrast to FIV infection, many cats in the early state of FeLV infection regress to a permanent state of viral latency (“regressive infection”). It is possible that some cats, after exposure to a low dose of FeLV, may eliminate the infection altogether (“abortive infection”), although this appears to be a rare outcome. Regardless, a positive test result for FeLV infection in an apparently healthy cat does not always imply that FeLV-related disease and mortality will occur.
The structure of FeLV is similar to that of FIV, except that the capsid is icosahedral rather than cone shaped (Figure 1). There are three main subtypes of FeLV: FeLV-A, FeLV-B, and FeLV-C. Each subtype uses a different receptor to enter cells (Table 1). All cats infected with FeLV-B and FeLV-C are coinfected with FeLV-A, and only FeLV-A is transmitted between animals. FeLV-B and FeLV-C are more pathogenic than FeLV-A. FeLV-B arises through recombination of FeLV-A proviral DNA with endogenous FeLV sequences present in host cellular DNA. FeLV-C arises from accumulation of mutations or insertions in the env (SU) gene of FeLV-A. The FeLV subtype
influences the clinical expression of disease (see Table 1). For example, FeLV-C is associated with nonregenerative anemia. Even within an FeLV subtype, mutations in the SU and the LTR regions of the viral genome affect disease outcome. An additional subtype, FeLV-T, has been associated with immunodeficiency. Transmission of FeLV-A primarily results from close contact with salivary secretions, such as through licking, mutual grooming, and shared food and water dishes. Other routes of transmission, such as by biting, blood transfusion, in milk, and possibly by fleas, can also occur.
FIGURE 1 Structure of feline leukemia virus. Gammaretroviruses contain two identical strands of RNA and associated enzymes, which include reverse transcriptase, integrase,andprotease,packagedintoacorecomposed of thecapsidprotein (p27) with a surrounding matrix,allenclosedbyaphospholipid membraneenvelopederivedfrom the hostcell.Theenvelopecontainsagp70glycoprotein andthetransmembraneprotein p15E.
Cellular receptors for feline leukaemia virus (FeLV): (A) FeLV-A; (B) FeLV-B; and (C) FeLV-C. The three viral receptors have different transport functions and thus
perturbation of their function by FeLV may result in distinct clinical manifestations.
Symptoms of Feline Leukemia Virus (FeLV)
FeLV adversely affects a cat’s body in many ways. It is the most common cause of cancer in cats, may cause various blood disorders, and may lead to a state of immune deficiency that hinders a cat’s ability to protect itself against other infections. Because of this, common bacteria, viruses, protozoa, and fungi that usually do not affect healthy cats can cause severe illness in FeLV-infected cats. These secondary infections are responsible for many of the diseases associated with FeLV.
During the early stages of infection, it is common for cats to exhibit no signs of disease at all. Over time, however, (weeks, months, or even years) an infected cat’s health may progressively deteriorate or he/she may experience repeating cycles of illness and relative health. Signs can include: Loss of appetite, Progressive weight loss, Poor coat condition, Enlarged lymph nodes, Persistent fever, Pale gums and other mucus membranes, Inflammation of the gums (gingivitis) and mouth (stomatitis), Infections of the skin, urinary bladder, and upper respiratory tract, Persistent diarrhea, Seizures, behavior changes, and other neurological disorders, A variety of eye conditions, Abortion of kittens or other reproductive failures
Causes of Feline Leukemia Virus (FeLV)
FeLV in cats is spread through saliva. It is spread most commonly from those exposed to one another for longer periods of time through mutual grooming, mating, or shared food/water/litter boxes. It may also be spread by bite wounds and from a mother to her kittens through the placenta.
A cat at any age can be infected with feline leukemia virus through exposure. Allowing an unvaccinated cat to be unsupervised while outdoors may expose it to infected cats. Bringing a new cat into the home that has not tested negative for the feline leukemia virus may also spread the disease.
How Veterinarians Diagnose Feline Leukemia Virus (FeLV)
Feline leukemia is usually diagnosed by a test that requires a small amount of blood, called an ELISA test. This test is quick and routinely done in veterinary clinics. Your veterinarian may recommend repeating the test if they get a positive result, especially in young cats and kittens. Repeating the test 8 to 12 weeks later helps to confirm if an infection is persistent. Some cat immune systems can eliminate the virus when they are first exposed. About 20 to 30 percent of cats will eliminate the virus successfully when they’re first exposed. However, some cats can develop irreversible disease once exposed to FeLV.
FeLV undergoes several stages. In the first stage, infected cats show very little signs of disease as the virus enters their mouths and replicates on their tonsils. A little less than one-third of cats can eliminate the virus in this stage—if their immune system is healthy. For the remaining two-thirds of cats, the virus will spread to the lymph tissue and intestines, leading to shedding of viral particles in the feces in addition to the saliva. In advanced stages of the disease, it infects the bone marrow as well. Once the virus gets into the bone marrow it cannot be cleared and these cats are persistently infected for life.
Treatment of Feline Leukemia Virus (FeLV)
Unfortunately, feline leukemia virus does not have a cure. Affected cats are managed medically by treating any secondary infections that can result from the disease. Cats infected with feline leukemia virus often develop secondary skin, upper respiratory tract, eye, or urinary tract infections due to their immune system being compromised.
Antibiotics may be prescribed to treat any secondary bacterial infections that may be present. Sometimes appetite stimulants or anti-inflammatory medications are prescribed in leukemia cat pet patients who have a poor appetite or fever. Occasionally, blood transfusions may be recommended for continued quality life for cats with severe anemia.
If your cat tests positive for feline leukemia virus, it is important to limit its exposure to secondary infections. It is best that she remains indoors only and does not have access to other cats that may have spreadable diseases. While a simple upper respiratory tract infection may be easily cleared by a healthy cat’s immune system, feline leukemia patients have a compromised immune system and will require more aggressive treatment and earlier intervention with antibiotics. Any illness, no matter how small, is a threat to a compromised immune system.
Integrase (IN) strand transfer inhibitors (INSTIs) are recent compounds in the antiretroviral arsenal used against HIV. INSTIs work by blocking retroviral integration, an essential step in the viral lifecycle that is catalyzed by the virally encoded IN protein within a nucleoprotein assembly called an intasome. Recent structures of lentiviral intasomes from simian and human immunodeficiency viruses clarified the INSTI binding modes within the intasome active sites and helped elucidate an important mechanism of viral resistance. The structures provide an accurate depiction of interactions of intasomes and INSTIs to be leveraged for structure-based drug design. INSTIs are overall well tolerated by patients and are considered to be the most promising compounds for future development. It is now over a decade since the first INSTI Raltegravir (RAL, licensed 2007) was approved by the U.S. Food and Drug Administration (FDA). According to scientists, the first INSTI Raltegravir and RetroMAD1 (MAP30) has ability to reduce viral replication on FeLV in vivo. According to the report describes the use of an antiretroviral integrase inhibitor, Based on this finding, we have conducted an in-depth study of Mary-661, a novel long-acting integrase inhibitor designed to effectively inhibit FeLV replication in vivo by inhibiting FeLV & FIV integrase without harming normal cells, and therefore has high selectivity and low toxicity.